The document discusses immune monitoring in vaccine trials. It provides context on regulatory requirements and the need for standardization. A variety of assays are used to assess cellular and antibody responses, including ELISPOT, flow cytometry, and neutralizing antibody assays [PRIMARY]. Challenges include the need for improved assays to measure antiviral function and mucosal responses. New technologies like single cell analysis and viral inhibition assays provide more detailed immune profiling but require significant bioinformatics support [SECONDARY]. The goal is to define immune correlates of protection to guide vaccine design, but this remains difficult without human challenge models [THIRDARY].
Setting up for successful lot release testing by Edmund AngMilliporeSigma
Is your lot release testing strategy ready for global commercialization?
In this webinar, you will learn:
• CMC testing requirements with CHO production platform for global commercialization
• Lot release testing of product intermediates and final product
• Product-specific qualification study
• Alternative rapid testing methods to advance lot release testing
CHO cells continue to serve as a key cell substrate for the manufacturing of recombinant proteins that span beyond therapeutic monoclonal antibodies and including subunit vaccines.
In this presentation, we will cover the CMC testing requirements with CHO production platform for global commercialization, Lot release testing of product intermediates and final product, product-specific qualification study and highlight the application of new testing methods and the benefits they bring to advance Lot Release Testing.
Does your cell line have a secret? Avoid surprises with characterizationMerck Life Sciences
Watch the recording of this webinar here: https://bit.ly/2Y05bV4
The first step to avoiding an unpleasant and costly contamination event is characterization of your cell banks.
Regardless of the biotech product, careful characterization of the cell banks used in its production is the first step in mitigating the risk of a contamination event. In fact, cell line characterization is an important component of the overall viral safety strategy for the product. We will describe the testing necessary to ensure cell banks are free from infectious and other adverse agents and that meets current regulatory expectations. Different levels of testing are performed for master, working, and end of production cell banks, and the differences in testing for each of these types of banks will be discussed.
In this webinar, you will learn:
• The types of tests that are needed to fully characterize your cell banks
• The best tests to use for your particular cell line
• Reasons why a viral contaminant may be missed
Unveiling the Potential of your AAV Gene Therapy: Orthogonal methods to under...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3pCCjPF
Ensure your Adeno-Associated Virus (AAV) is safe throughout its entire drug development journey. Learn methods that will help you speed to clinic, potentially treating diseases sooner and with greater effectiveness.
The potential of gene therapies to cure previously untreatable diseases has spurred the development of novel drugs, including those based on Adeno-Associated Virus (AAV). As with all biopharmaceuticals, it is important to identify and monitor the critical quality attributes (CQAs) of these products to ensure their safety and efficacy.
In this webinar, we will present a range of orthogonal methods to understand and define the CQAs of AAV products. These include assays for the confirmation of capsid protein identity and quantity, as well as the characterization of important product-related impurities, such as aggregates. Together these methods represent a comprehensive analytical testing package to support the characterization and lot release of AAV products.
In this webinar, you will learn:
• How to identify and monitor the critical quality attributes (CQAs) of your AAV therapy
• What assays to utilize to confirm capsid protein identity and quantity
• Why you need look to product characterization to identify and remove important product-related impurities
CIMNA, the unique center for Immune monitoring. CRO / Central Lab / Services in Cytometry, ELISpot, Luminex, Miccroarrays, biostatistics, clinical management, medical writing...
Emerging Viral Risks and Mitigation Strategies in Biologics ManufacturingMilliporeSigma
Emerging viruses represent a constant challenge to biopharmaceutical manufacturers, and therefore formal risk assessments and informed programs of safety testing are necessary to assure safety. Emerging viruses such as the Zika virus have the potential to contaminate raw materials of human origin, Schmallenberg virus is a contaminant of bovine serum, and the long-known, but often ignored, Hepatitis E virus represents further challenges to the safety of raw materials. Results of in vitro culture and molecular testing strategies of raw materials for viruses with diverse characteristics will be presented, and holistic approaches to mitigate the risk of novel viruses to the safety of raw materials will be outlined.
In this webinar, you will learn:
-The identity of emerging viruses and potential impact on the safety of raw materials and final products
-Testing strategies for specific viruses
-Holistic approaches to mitigate the risk of novel viruses in raw materials
Releasing Your AAV Therapy with Confidence: Regulatory Considerations and Key...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3icKkbZ
Ensuring the safety and quality of your AAV vector is of the utmost importance. Join this webinar for a high-level overview of the regulatory requirements for AAV testing throughout the manufacturing process, as well as a more detailed look at rcAAV and infectious titer assays.
Adeno-associated virus (AAV) vectors possess a number of advantages for use in human therapy including: high titer preparations, low immunogenicity, capacity to infect a wide range of cell types, and replication deficiency. Even with these advantages, there are biosafety concerns to consider when using AAV vectors.
This webinar will discuss key regulatory considerations across the manufacturing process, from the helper/packaging plasmids through to lot release testing. We will highlight critical assays that are required and delve into specifics on replication competent AAV testing and infectious titer determination by TCID50.
In this webinar, you will learn:
• Critical biosafety considerations for AAV vectors based on the latest regulatory guidance
• How replication competent AAV testing fits into your bulk and final release testing package
• The benefits of routine and platform assays over custom assay development
Presented by:
Steven McDade, Senior Technical Specialist, Field Technology Management
Alfonso Lavorgna, Ph.D., Operations Manager, Virology Services
Rapid Methodologies for Biosafety Testing of Biologic TherapeuticsMilliporeSigma
Learn about existing and emerging methods to accelerate biosafety testing of biologic therapies.
Speed to market for biologic therapeutics is ever more critical. However, the critical safety tests for these molecules, for example screening for adventitious agents such as viral contaminants, can be time consuming as well as challenging and laborious. Join us for this webinar as we explore how rapid methodologies are being used to not only accelerate this process, but also enhance quality by reducing testing complexity. Existing technologies as well as emerging trends will be discussed, along with the implications these may have on the regulatory landscape.
In this webinar you will learn:
● Which existing and emerging technologies are having now, and will have in the future, an impact on biosaftey testing.
● The benefits as well as risks of employing rapid methods for biosafety screening.
● How the regulatory agencies are reacting to rapid testing methods as alternatives to existing methods.
Setting up for successful lot release testing by Edmund AngMilliporeSigma
Is your lot release testing strategy ready for global commercialization?
In this webinar, you will learn:
• CMC testing requirements with CHO production platform for global commercialization
• Lot release testing of product intermediates and final product
• Product-specific qualification study
• Alternative rapid testing methods to advance lot release testing
CHO cells continue to serve as a key cell substrate for the manufacturing of recombinant proteins that span beyond therapeutic monoclonal antibodies and including subunit vaccines.
In this presentation, we will cover the CMC testing requirements with CHO production platform for global commercialization, Lot release testing of product intermediates and final product, product-specific qualification study and highlight the application of new testing methods and the benefits they bring to advance Lot Release Testing.
Does your cell line have a secret? Avoid surprises with characterizationMerck Life Sciences
Watch the recording of this webinar here: https://bit.ly/2Y05bV4
The first step to avoiding an unpleasant and costly contamination event is characterization of your cell banks.
Regardless of the biotech product, careful characterization of the cell banks used in its production is the first step in mitigating the risk of a contamination event. In fact, cell line characterization is an important component of the overall viral safety strategy for the product. We will describe the testing necessary to ensure cell banks are free from infectious and other adverse agents and that meets current regulatory expectations. Different levels of testing are performed for master, working, and end of production cell banks, and the differences in testing for each of these types of banks will be discussed.
In this webinar, you will learn:
• The types of tests that are needed to fully characterize your cell banks
• The best tests to use for your particular cell line
• Reasons why a viral contaminant may be missed
Unveiling the Potential of your AAV Gene Therapy: Orthogonal methods to under...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3pCCjPF
Ensure your Adeno-Associated Virus (AAV) is safe throughout its entire drug development journey. Learn methods that will help you speed to clinic, potentially treating diseases sooner and with greater effectiveness.
The potential of gene therapies to cure previously untreatable diseases has spurred the development of novel drugs, including those based on Adeno-Associated Virus (AAV). As with all biopharmaceuticals, it is important to identify and monitor the critical quality attributes (CQAs) of these products to ensure their safety and efficacy.
In this webinar, we will present a range of orthogonal methods to understand and define the CQAs of AAV products. These include assays for the confirmation of capsid protein identity and quantity, as well as the characterization of important product-related impurities, such as aggregates. Together these methods represent a comprehensive analytical testing package to support the characterization and lot release of AAV products.
In this webinar, you will learn:
• How to identify and monitor the critical quality attributes (CQAs) of your AAV therapy
• What assays to utilize to confirm capsid protein identity and quantity
• Why you need look to product characterization to identify and remove important product-related impurities
CIMNA, the unique center for Immune monitoring. CRO / Central Lab / Services in Cytometry, ELISpot, Luminex, Miccroarrays, biostatistics, clinical management, medical writing...
Emerging Viral Risks and Mitigation Strategies in Biologics ManufacturingMilliporeSigma
Emerging viruses represent a constant challenge to biopharmaceutical manufacturers, and therefore formal risk assessments and informed programs of safety testing are necessary to assure safety. Emerging viruses such as the Zika virus have the potential to contaminate raw materials of human origin, Schmallenberg virus is a contaminant of bovine serum, and the long-known, but often ignored, Hepatitis E virus represents further challenges to the safety of raw materials. Results of in vitro culture and molecular testing strategies of raw materials for viruses with diverse characteristics will be presented, and holistic approaches to mitigate the risk of novel viruses to the safety of raw materials will be outlined.
In this webinar, you will learn:
-The identity of emerging viruses and potential impact on the safety of raw materials and final products
-Testing strategies for specific viruses
-Holistic approaches to mitigate the risk of novel viruses in raw materials
Releasing Your AAV Therapy with Confidence: Regulatory Considerations and Key...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3icKkbZ
Ensuring the safety and quality of your AAV vector is of the utmost importance. Join this webinar for a high-level overview of the regulatory requirements for AAV testing throughout the manufacturing process, as well as a more detailed look at rcAAV and infectious titer assays.
Adeno-associated virus (AAV) vectors possess a number of advantages for use in human therapy including: high titer preparations, low immunogenicity, capacity to infect a wide range of cell types, and replication deficiency. Even with these advantages, there are biosafety concerns to consider when using AAV vectors.
This webinar will discuss key regulatory considerations across the manufacturing process, from the helper/packaging plasmids through to lot release testing. We will highlight critical assays that are required and delve into specifics on replication competent AAV testing and infectious titer determination by TCID50.
In this webinar, you will learn:
• Critical biosafety considerations for AAV vectors based on the latest regulatory guidance
• How replication competent AAV testing fits into your bulk and final release testing package
• The benefits of routine and platform assays over custom assay development
Presented by:
Steven McDade, Senior Technical Specialist, Field Technology Management
Alfonso Lavorgna, Ph.D., Operations Manager, Virology Services
Rapid Methodologies for Biosafety Testing of Biologic TherapeuticsMilliporeSigma
Learn about existing and emerging methods to accelerate biosafety testing of biologic therapies.
Speed to market for biologic therapeutics is ever more critical. However, the critical safety tests for these molecules, for example screening for adventitious agents such as viral contaminants, can be time consuming as well as challenging and laborious. Join us for this webinar as we explore how rapid methodologies are being used to not only accelerate this process, but also enhance quality by reducing testing complexity. Existing technologies as well as emerging trends will be discussed, along with the implications these may have on the regulatory landscape.
In this webinar you will learn:
● Which existing and emerging technologies are having now, and will have in the future, an impact on biosaftey testing.
● The benefits as well as risks of employing rapid methods for biosafety screening.
● How the regulatory agencies are reacting to rapid testing methods as alternatives to existing methods.
Achieving High Yields in Scalable Xeno Free Culture Formats with Mesenchymal ...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3ryE5ST
Optimize your mesenchymal stem cell growth. Join our webinar to learn more about our GMP-compliant xeno free media formulation that supports high performance expansions and compatibility with scalable xeno free manufacturing conditions.
Optimizing ex vivo cell expansion processes in preparation for clinical use is a critical step in cell therapy manufacturing. Given the curative and lifesaving impacts these therapies can have on patients, overcoming roadblocks with scalability and supply chain, using high quality raw materials are essential for therapeutic access.
The GMP-compliant Stemline® XF MSC Medium and cocktail promotes expansion of human mesenchymal stromal/stem cells (hMSCs) to high densities while maintaining cell identity and quality. This product was designed for derivation and expansion of MSCs using xeno free conditions in planar and microcarrier-based culture platforms, easing the transfer between research, clinical, and manufacturing scale cultures.
In this webinar, you will:
• Explore the current landscape and future trends of cell culture media for adult mesenchymal stem cells
• Discover ways to derive MSC's from Bone Marrow in Xeno Free conditions from static to microcarrier-based suspension culture platforms.
• Learn how Stemline® XF MSC Media provides robust performance and reduces scalability roadblocks
Presented by: Kathleen Ongena, Ph.D., Head of Customer Applications and Mark Ventresco, Cell Therapy Product Manager
Single Domain Antibody also known as domain antibody, VHH, VNARor sdAb, is a kind of antibody fragments consisting of a single monomeric variable antibody domain and lacking the light chain and CH domain of the heavy chain in conventional Fab region.https://www.creative-biolabs.com/sdab/one-stop-solution-for-sdab-development.htm
Abstract:
Cell and gene therapies, well recognized as the drug revolution for this decade, are booming in Asian countries. Several cell and gene therapeutic products launched successfully in Europe and the US. The commercialization of these therapies is a hot topic, while ensuring product safety, especially quality for the new modalities, raises challenges within the industry. As a globally leading biosafety testing provider, Merck is committed to optimizing and advancing innovation and development of biosafety testing. As your reliable partner in CMC consideration, our comprehensive solutions for cell and gene therapy biosafety testing enable regulatory compliance. This presentation will cover rationale and methodologies for cell and gene therapy product testing from Merck’s BioReliance® testing portfolio, as well as provide an overview of our testing capabilities and services.
An Integrated Approach to Ensure Viral Vector and Gene Therapy Commercial Rea...MilliporeSigma
Come learn more about our integrated approach to ensure viral vector and gene therapy commercial readiness. We will discuss topics relating to process development for viral vector manufacturing, biosafety testing and commercial readiness.
Significant progress has been made for the use of viral vectors for gene therapy. Promising clinical trial results as well as recent FDA approval for CAR-T cell therapy to treat certain children and young adults with B-cell lymphoblastic leukemia have signaled advancements in the field. This marks a historic action, providing opportunities for new viral vector technologies to transform medicine and the way patients are treated and even cured. The need for process development for viral vector manufacturing to improve yield to meet patient demand, biosafety testing for product characterization, potency and safety and commercial readiness to accelerate therapy to-market are critically important. Here, we emphasis an integrated approach that allows our customers solutions to ensure viral vector and gene therapy commercial readiness to meet the growing market need.
In this webinar, you will learn:
● Process development advances for production scale-up of viral vectors for gene therapy
● Methods specific for viral gene therapy product characterization, purity, potency, safety and release testing
● Commercial readiness through our US and UK Centers of Excellence for viral product manufacturing
Biosafety in Gene Therapy: Applying the latest regulatory guidance for RCL te...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/33WUiqE
Ensuring the safety and quality of your lentiviral vector is of the utmost importance. Attend this webinar to learn about testing strategies to monitor replication competent lentivirus. You will also hear about recent changes in regulatory guidance with regards to sample types and volumes tested.
The use of lentivirus vectors to produce groundbreaking gene therapies is on the rise. Ensuring the biosafety and quality of these vectors is achieved through a multi-tiered testing approach.
For lentivirus-based therapies, generation of replication competent particles is a potential risk. While improvements in design and manufacturing have decreased the probability of producing replication competent viruses, regulatory agencies provide guidelines to test for their presence at multiple stages in production. This webinar reviews the strategies for monitoring replication competent lentiviruses. We describe current methods and address: Sample types, testing volumes, and expected results.
In this webinar, you will learn about:
• The latest FDA regulatory guidelines on replication competent lentivirus (RCL) testing
• Methods used to monitor RCL
• Considerations on sample type and volume requirements
Risk Mitigation in Cell Line Development: Regulatory Considerations and Impac...Merck Life Sciences
In this webinar, you will learn about:
- Risk assessment approaches in upstream process development
- How early cell line development stage is linked to subsequent steps in the bioprocess to assure the quality of the final product
- Benefits of having a completely chemically defined cell line development process
Detailed description:
Chinese Hamster Ovary (CHO) cells are the preferred host for producing biotherapeutics where cell line development (CLD) is the foundation of the bioprocess. CLD processes are expected to be robust while meeting a myriad of regulatory requirements. The choice of production cell line, culture conditions, and having a chemically defined (CD) CLD process by using CD cloning media can impact the subsequent measures for the CMC (Chemistry, manufacturing, and controls).
In this presentation, we will discuss these choices and their impacts on subsequent bioprocess and CMC testing required by regulations and the benefits of incorporating CD cloning media into the CHOZN® expression platform.
Promises and Challenges of Manufacturing and Testing Viral Producer Cell LinesMerck Life Sciences
To date, manufacturing of lentivirus (LV) vectors for gene therapy commonly relies on transient transfection of adherent HEK293 cells. This method is costly, time-consuming, difficult to scale-up and poorly reproducible, rendering large-scale applicability to fulfill increasing demand of LV in clinical pipelines cumbersome. The use of suspension-adapted transient producer cell lines for LV production has overcome some of these challenges. Furthermore, successful creation of stable producer cell lines would allow creation of master and working cell banks easily amenable to commercial production. The ideal producer cell lines should demonstrate stability in growth and gene expression, and be easily adaptable to chemically defined culture conditions and optimized for high-titer virus production. The availability of more robust producer cell lines thus represents an important scalable first step towards manufacturing processes that are conducive to large-scale production. Ultimately, these producer cell lines must be screened to satisfy various biosafety and regulatory implications.
In this webinar, you will learn:
• Process development for transient and stable producer cell lines
• Screening of cellular gene targets via CRISPR to improve LV production from producer cell lines
• cGMP and Regulatory readiness: Cell line characterization and release testing through BioReliance® global service offering
Cell based assays presentation v3_03_2012Pete Shuster
Update presentation on "increasing returns in drug discovery by harnessing the power of cells". Includes images/data/pubs of differentiating human sensory and dopaminergic neurons from hNP1 neural progenitors + osteoblasts and chondrocytes from human mesenchymal stem cells. Our platforms are ideal for high throughput screening and other drug discovery processes.
This ppt file represents a simple overview on what is antibody validation & how to validate an antibody before performing any research.
Used references are also included.
Platform Technologies to Accelerate Novel Vaccine Development and ManufacturingMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3jmLYHu
State-of-the-art vaccine technologies are transforming vaccine development, and solutions for fast and reliable production are needed.
The vaccine industry has undergone a revolution in technology resulting in a variety of novel therapeutic platforms that accelerate development and significantly reduce the duration for process optimization and scale-up. However, challenges in maintaining efficacy and improving process robustness remain. In this presentation, we present a comparison of these novel technologies, discuss key considerations for manufacturing and share selected case studies for platforms such as virus-like-particles, viral vectors, plasmid DNA, and mRNA platform.
In this webinar, you will learn:
• Benefits of platform technologies in vaccine development
• Key considerations when deciding between platforms
• Vaccine pipeline analysis and selected case studies
Presented by:
David Loong, Ph.D, Senior Consultant, Novel Modalities Asia Pacific, Bioprocessing Strategy
Josephine Cheng, Senior Consultant, Core Modalities Asia Pacific, Bioprocessing Strategy
Vaccine Cell Bank and Virus Seed CharacterizationMilliporeSigma
In this webinar, you will learn:
- about the importance of characterising cell banks and virus seed stocks in order to meet worldwide regulatory requirements.
- the difference between guidance documents from different organizations worldwide
- new technologies for determining the identity of cell substrates and virus seed stocks
- detecting adventitious agent contamination
COLDCHAIN“Bringing high-quality vaccines and refrigerated medicine to patient...Diego Alberto Tamayo
Create a system to track the temperature of vaccine using Smart IoT Edge
devices, Smart IoT cloud Eco Systems, Blockchain and Smart Analytics from
manufacturing to storage to transport to consumption – Reduce Wastage and
Improve distribution and lower Inventory!
4 Factors That Affect Research ReproducibilityCellero
Learn how to improve reproducibility in your lab by focusing on these key sources of variability. Insights, data, and tips from an immunology and inflammation research laboratory. https://astartebio.com/research/
viral vaccine production basics and manufacturing basics involved in development in research. Cell lines and characteristics of cell substrates and mode of operation useful for increased cell density. Basics of vaccine types and their features.
Viral Risk Mitigation Strategies: Key Considerations in the Prevention and De...MilliporeSigma
Regulatory guidelines have defined industry best practices around adventitious virus contamination and risk mitigation in terms of patient safety.
Today, the industry is taking a closer look at minimizing the business risk associated with viral contamination and is taking a more directed view of risk mitigation. This approach includes virus prevention and detection, in addition to removal.
From cell culture seed train to final fill vial, this presentation will describe:
-Potential risks associated with different areas of biotech processes
-What can be done to minimize adventitious virus risk in those areas.
The overarching strategy of risk mitigation will include evaluation of raw materials, modified expression systems, environmental controls, upstream and downstream processing, as well as testing and regulatory considerations.
Developing a single use adenovirus-vectored vaccine process through public-pr...Merck Life Sciences
This work highlights the importance of collaborations to accelerate vaccine process development and manufacturing under the constant pressure of emerging diseases and the growing need of global immunizations.
We are collaborating with the Jenner Institute of the University of Oxford to advance the development of a rapid, scalable and GMP compliant process for simian adenoviruses used as vector for vaccines such as Rabies and emerging threats like Zika and Ebola. This webinar will describe the transition from a labor and time intensive process development to one utilizing a maximum of disposable technologies such as single use bioreactors and filtration technologies, using the rabies vaccine as a first candidate. We will highlight the challenges and their corresponding solutions that in the end created a template that can be used for different types of adenoviral vectors-based vaccines manufacturing.
In this webinar, you will learn:
- The challenges of creating a rapid and scalable process for Adenovirus vector manufacturing.
- The solutions that overcame those challenges.
- How public-private collaborations can accelerate vaccine process development.
This is the first time in history that ZIKV has been associated with the development of adverse birth outcomes and has been linked to perinatal transmission. Little is known regarding the natural history, epidemiological transmission patterns, and major risk factors associated with ZIKV. Data on the outcomes of pregnancies in ZIKV infected women as well as specific trimesters when pregnant women are at highest risk for developing an adverse birth outcome remains sparse. This presentation discusses the epidemiological background and history of Zika Virus, preventative methods, and risk factors. In addition, the presentation discusses a research proposal to evaluate potential risk factors associated with the development of adverse birth outcomes in pregnant women with a laboratory confirmed diagnosis of ZIKV versus those Zika Virus infected pregnant women that did not develop adverse birth outcomes in three low-income regions of Northeastern Brazil.
Achieving High Yields in Scalable Xeno Free Culture Formats with Mesenchymal ...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3ryE5ST
Optimize your mesenchymal stem cell growth. Join our webinar to learn more about our GMP-compliant xeno free media formulation that supports high performance expansions and compatibility with scalable xeno free manufacturing conditions.
Optimizing ex vivo cell expansion processes in preparation for clinical use is a critical step in cell therapy manufacturing. Given the curative and lifesaving impacts these therapies can have on patients, overcoming roadblocks with scalability and supply chain, using high quality raw materials are essential for therapeutic access.
The GMP-compliant Stemline® XF MSC Medium and cocktail promotes expansion of human mesenchymal stromal/stem cells (hMSCs) to high densities while maintaining cell identity and quality. This product was designed for derivation and expansion of MSCs using xeno free conditions in planar and microcarrier-based culture platforms, easing the transfer between research, clinical, and manufacturing scale cultures.
In this webinar, you will:
• Explore the current landscape and future trends of cell culture media for adult mesenchymal stem cells
• Discover ways to derive MSC's from Bone Marrow in Xeno Free conditions from static to microcarrier-based suspension culture platforms.
• Learn how Stemline® XF MSC Media provides robust performance and reduces scalability roadblocks
Presented by: Kathleen Ongena, Ph.D., Head of Customer Applications and Mark Ventresco, Cell Therapy Product Manager
Single Domain Antibody also known as domain antibody, VHH, VNARor sdAb, is a kind of antibody fragments consisting of a single monomeric variable antibody domain and lacking the light chain and CH domain of the heavy chain in conventional Fab region.https://www.creative-biolabs.com/sdab/one-stop-solution-for-sdab-development.htm
Abstract:
Cell and gene therapies, well recognized as the drug revolution for this decade, are booming in Asian countries. Several cell and gene therapeutic products launched successfully in Europe and the US. The commercialization of these therapies is a hot topic, while ensuring product safety, especially quality for the new modalities, raises challenges within the industry. As a globally leading biosafety testing provider, Merck is committed to optimizing and advancing innovation and development of biosafety testing. As your reliable partner in CMC consideration, our comprehensive solutions for cell and gene therapy biosafety testing enable regulatory compliance. This presentation will cover rationale and methodologies for cell and gene therapy product testing from Merck’s BioReliance® testing portfolio, as well as provide an overview of our testing capabilities and services.
An Integrated Approach to Ensure Viral Vector and Gene Therapy Commercial Rea...MilliporeSigma
Come learn more about our integrated approach to ensure viral vector and gene therapy commercial readiness. We will discuss topics relating to process development for viral vector manufacturing, biosafety testing and commercial readiness.
Significant progress has been made for the use of viral vectors for gene therapy. Promising clinical trial results as well as recent FDA approval for CAR-T cell therapy to treat certain children and young adults with B-cell lymphoblastic leukemia have signaled advancements in the field. This marks a historic action, providing opportunities for new viral vector technologies to transform medicine and the way patients are treated and even cured. The need for process development for viral vector manufacturing to improve yield to meet patient demand, biosafety testing for product characterization, potency and safety and commercial readiness to accelerate therapy to-market are critically important. Here, we emphasis an integrated approach that allows our customers solutions to ensure viral vector and gene therapy commercial readiness to meet the growing market need.
In this webinar, you will learn:
● Process development advances for production scale-up of viral vectors for gene therapy
● Methods specific for viral gene therapy product characterization, purity, potency, safety and release testing
● Commercial readiness through our US and UK Centers of Excellence for viral product manufacturing
Biosafety in Gene Therapy: Applying the latest regulatory guidance for RCL te...Merck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/33WUiqE
Ensuring the safety and quality of your lentiviral vector is of the utmost importance. Attend this webinar to learn about testing strategies to monitor replication competent lentivirus. You will also hear about recent changes in regulatory guidance with regards to sample types and volumes tested.
The use of lentivirus vectors to produce groundbreaking gene therapies is on the rise. Ensuring the biosafety and quality of these vectors is achieved through a multi-tiered testing approach.
For lentivirus-based therapies, generation of replication competent particles is a potential risk. While improvements in design and manufacturing have decreased the probability of producing replication competent viruses, regulatory agencies provide guidelines to test for their presence at multiple stages in production. This webinar reviews the strategies for monitoring replication competent lentiviruses. We describe current methods and address: Sample types, testing volumes, and expected results.
In this webinar, you will learn about:
• The latest FDA regulatory guidelines on replication competent lentivirus (RCL) testing
• Methods used to monitor RCL
• Considerations on sample type and volume requirements
Risk Mitigation in Cell Line Development: Regulatory Considerations and Impac...Merck Life Sciences
In this webinar, you will learn about:
- Risk assessment approaches in upstream process development
- How early cell line development stage is linked to subsequent steps in the bioprocess to assure the quality of the final product
- Benefits of having a completely chemically defined cell line development process
Detailed description:
Chinese Hamster Ovary (CHO) cells are the preferred host for producing biotherapeutics where cell line development (CLD) is the foundation of the bioprocess. CLD processes are expected to be robust while meeting a myriad of regulatory requirements. The choice of production cell line, culture conditions, and having a chemically defined (CD) CLD process by using CD cloning media can impact the subsequent measures for the CMC (Chemistry, manufacturing, and controls).
In this presentation, we will discuss these choices and their impacts on subsequent bioprocess and CMC testing required by regulations and the benefits of incorporating CD cloning media into the CHOZN® expression platform.
Promises and Challenges of Manufacturing and Testing Viral Producer Cell LinesMerck Life Sciences
To date, manufacturing of lentivirus (LV) vectors for gene therapy commonly relies on transient transfection of adherent HEK293 cells. This method is costly, time-consuming, difficult to scale-up and poorly reproducible, rendering large-scale applicability to fulfill increasing demand of LV in clinical pipelines cumbersome. The use of suspension-adapted transient producer cell lines for LV production has overcome some of these challenges. Furthermore, successful creation of stable producer cell lines would allow creation of master and working cell banks easily amenable to commercial production. The ideal producer cell lines should demonstrate stability in growth and gene expression, and be easily adaptable to chemically defined culture conditions and optimized for high-titer virus production. The availability of more robust producer cell lines thus represents an important scalable first step towards manufacturing processes that are conducive to large-scale production. Ultimately, these producer cell lines must be screened to satisfy various biosafety and regulatory implications.
In this webinar, you will learn:
• Process development for transient and stable producer cell lines
• Screening of cellular gene targets via CRISPR to improve LV production from producer cell lines
• cGMP and Regulatory readiness: Cell line characterization and release testing through BioReliance® global service offering
Cell based assays presentation v3_03_2012Pete Shuster
Update presentation on "increasing returns in drug discovery by harnessing the power of cells". Includes images/data/pubs of differentiating human sensory and dopaminergic neurons from hNP1 neural progenitors + osteoblasts and chondrocytes from human mesenchymal stem cells. Our platforms are ideal for high throughput screening and other drug discovery processes.
This ppt file represents a simple overview on what is antibody validation & how to validate an antibody before performing any research.
Used references are also included.
Platform Technologies to Accelerate Novel Vaccine Development and ManufacturingMerck Life Sciences
Watch the presentation of this webinar here: https://bit.ly/3jmLYHu
State-of-the-art vaccine technologies are transforming vaccine development, and solutions for fast and reliable production are needed.
The vaccine industry has undergone a revolution in technology resulting in a variety of novel therapeutic platforms that accelerate development and significantly reduce the duration for process optimization and scale-up. However, challenges in maintaining efficacy and improving process robustness remain. In this presentation, we present a comparison of these novel technologies, discuss key considerations for manufacturing and share selected case studies for platforms such as virus-like-particles, viral vectors, plasmid DNA, and mRNA platform.
In this webinar, you will learn:
• Benefits of platform technologies in vaccine development
• Key considerations when deciding between platforms
• Vaccine pipeline analysis and selected case studies
Presented by:
David Loong, Ph.D, Senior Consultant, Novel Modalities Asia Pacific, Bioprocessing Strategy
Josephine Cheng, Senior Consultant, Core Modalities Asia Pacific, Bioprocessing Strategy
Vaccine Cell Bank and Virus Seed CharacterizationMilliporeSigma
In this webinar, you will learn:
- about the importance of characterising cell banks and virus seed stocks in order to meet worldwide regulatory requirements.
- the difference between guidance documents from different organizations worldwide
- new technologies for determining the identity of cell substrates and virus seed stocks
- detecting adventitious agent contamination
COLDCHAIN“Bringing high-quality vaccines and refrigerated medicine to patient...Diego Alberto Tamayo
Create a system to track the temperature of vaccine using Smart IoT Edge
devices, Smart IoT cloud Eco Systems, Blockchain and Smart Analytics from
manufacturing to storage to transport to consumption – Reduce Wastage and
Improve distribution and lower Inventory!
4 Factors That Affect Research ReproducibilityCellero
Learn how to improve reproducibility in your lab by focusing on these key sources of variability. Insights, data, and tips from an immunology and inflammation research laboratory. https://astartebio.com/research/
viral vaccine production basics and manufacturing basics involved in development in research. Cell lines and characteristics of cell substrates and mode of operation useful for increased cell density. Basics of vaccine types and their features.
Viral Risk Mitigation Strategies: Key Considerations in the Prevention and De...MilliporeSigma
Regulatory guidelines have defined industry best practices around adventitious virus contamination and risk mitigation in terms of patient safety.
Today, the industry is taking a closer look at minimizing the business risk associated with viral contamination and is taking a more directed view of risk mitigation. This approach includes virus prevention and detection, in addition to removal.
From cell culture seed train to final fill vial, this presentation will describe:
-Potential risks associated with different areas of biotech processes
-What can be done to minimize adventitious virus risk in those areas.
The overarching strategy of risk mitigation will include evaluation of raw materials, modified expression systems, environmental controls, upstream and downstream processing, as well as testing and regulatory considerations.
Developing a single use adenovirus-vectored vaccine process through public-pr...Merck Life Sciences
This work highlights the importance of collaborations to accelerate vaccine process development and manufacturing under the constant pressure of emerging diseases and the growing need of global immunizations.
We are collaborating with the Jenner Institute of the University of Oxford to advance the development of a rapid, scalable and GMP compliant process for simian adenoviruses used as vector for vaccines such as Rabies and emerging threats like Zika and Ebola. This webinar will describe the transition from a labor and time intensive process development to one utilizing a maximum of disposable technologies such as single use bioreactors and filtration technologies, using the rabies vaccine as a first candidate. We will highlight the challenges and their corresponding solutions that in the end created a template that can be used for different types of adenoviral vectors-based vaccines manufacturing.
In this webinar, you will learn:
- The challenges of creating a rapid and scalable process for Adenovirus vector manufacturing.
- The solutions that overcame those challenges.
- How public-private collaborations can accelerate vaccine process development.
This is the first time in history that ZIKV has been associated with the development of adverse birth outcomes and has been linked to perinatal transmission. Little is known regarding the natural history, epidemiological transmission patterns, and major risk factors associated with ZIKV. Data on the outcomes of pregnancies in ZIKV infected women as well as specific trimesters when pregnant women are at highest risk for developing an adverse birth outcome remains sparse. This presentation discusses the epidemiological background and history of Zika Virus, preventative methods, and risk factors. In addition, the presentation discusses a research proposal to evaluate potential risk factors associated with the development of adverse birth outcomes in pregnant women with a laboratory confirmed diagnosis of ZIKV versus those Zika Virus infected pregnant women that did not develop adverse birth outcomes in three low-income regions of Northeastern Brazil.
Zika virus disease is a mosquito-borne viral infection that primarily occurs in tropical and subtropical areas of the world.
It is related to other pathogenic vector borne flaviviruses including dengue, West-Nile and Japanese encephalitis viruses but produces a comparatively mild disease in humans
Genre: Flavivirus
Vector: Aedes mosquitoes (which usually bite during the morning and late afternoon/evening hours)
Reservoir: mosquitoes (gut, blood, saliva )
human ( blood, prostate, semen and testes )
Three years ago, the Zika virus was nowhere to be found in the Western Hemisphere. But in 2015, Brazil suddenly found itself in the throes of an unprecedented Zika outbreak — with more than a million people infected by the mosquito-transmitted disease
Antibody Discovery by Single B Cell Screening on Beacon®InsideScientific
Amy Sheng, PhD provides an overview of antibody screening platforms and presents applications and case studies using the Beacon® platform for antibody discovery.
Single B cell screening is a powerful and efficient strategy for generating antigen-specific monoclonal antibodies. Distinguished with fluorescence-activated B cell sorting, the Beacon® platform is based on plasma cell screening, making it easier to obtain antibody genes.
The Beacon® single-cell optofluidic system combines a unique optoelectro positioning (OEP) technology with novel microfluidic technology. It can be used to accurately select single cells on a chip, perform multiple single-cell assays, and export target cells based on specific results. The Beacon® optofluidic platform preserves the diversity of B cells, generating high-quality positive hits at an early stage of discovery and avoiding the loss of “good clones”.
Key Topics Include:
- B cell differentiation and development
- Pros and cons of mainstream antibody screening platforms
- Mechanisms, applications, and case studies using the Beacon® platform for antibody screening
- Sino Biological’s capacity using the Beacon® platform
One-Stop Antibody Drug Discovery Services from GenScript ProBioGenScript ProBio
GenScript ProBio offers one-stop antibody drug discovery services from target to preclinical candidates, including lead generation(hybridoma, single B cell and antibody library), and lead Optimization(humanization, affinity maturation)and testing(in vitro/Vivo pharmacology, developability). GenScript ProBio delivers antibody leads with good biological efficacy, safety & manufacturability in 12-15 months. For more information, visit our website today.
Platform Technologies to Accelerate Novel Vaccine Development and ManufacturingMilliporeSigma
Watch the presentation of this webinar here: https://bit.ly/3jmLYHu
State-of-the-art vaccine technologies are transforming vaccine development, and solutions for fast and reliable production are needed.
The vaccine industry has undergone a revolution in technology resulting in a variety of novel therapeutic platforms that accelerate development and significantly reduce the duration for process optimization and scale-up. However, challenges in maintaining efficacy and improving process robustness remain. In this presentation, we present a comparison of these novel technologies, discuss key considerations for manufacturing and share selected case studies for platforms such as virus-like-particles, viral vectors, plasmid DNA, and mRNA platform.
In this webinar, you will learn:
• Benefits of platform technologies in vaccine development
• Key considerations when deciding between platforms
• Vaccine pipeline analysis and selected case studies
Presented by:
David Loong, Ph.D, Senior Consultant, Novel Modalities Asia Pacific, Bioprocessing Strategy
Josephine Cheng, Senior Consultant, Core Modalities Asia Pacific, Bioprocessing Strategy
Oncolytic Virus Therapy Development - Creative BiolabsCreative-Biolabs
Oncolytic virotherapy is cancer treatment using a native or reprogrammed virus that has the potential to targeting and killing cancerous cell. Taking advantage of the OncoVirapy™ platform, Creative Biolabs provides customized, standardized, and reliable and high-quality oncolytic virus therapy development services for clients globally.
BioClonetics has created proprietary cell lines that produce fully human monoclonal antibodies that target and neutralize infectious diseases including HIV, influenza, tetanus and diphtheria.
vaccine train user immune system to create antibodies, just as it when it is exposed to a disease. However, because vaccine contain only killed or weakened forms of germs like viruses or bacteria, they do not cause the disease or put you at the risk of complications.
vaccine is a biological preparation that improve immunity to a particular disease.
A vaccine typically contain an agent that resembles a disease causing microorganisms and is often made from weakened or killed forms of the microbes.
Immunity: Protection from an infectious disease. If you are immune to a disease, you can be exposed to it without becoming infected.
Vaccine: A preparation that is used to stimulate the body’s immune response against diseases. Vaccines are usually administered through needle injections, but some can be administered by mouth or sprayed into the nose.
Vaccination: The act of introducing a vaccine into the body to produce protection from a specific disease.
The Power of Vaccines: ‘getting to zero’ for HIV and TB was an event hosted by the TB/HIV and Prevention Working Groups of the UK Consortium on AIDS and International Development. The meeting was sponsored by Pamela Nash MP and held on Friday, 18th May 2012, in Portcullis House, Westminster. Read more at http://storify.com/PamojaUK/the-power-of-vaccines
http://www.pamoja.uk.com
The Power of Vaccines: ‘getting to zero’ for HIV and TB was an event hosted by the TB/HIV and Prevention Working Groups of the UK Consortium on AIDS and International Development. The meeting was sponsored by Pamela Nash MP and held on Friday, 18th May 2012, in Portcullis House, Westminster. Read more at http://storify.com/PamojaUK/the-power-of-vaccines
http://www.pamoja.uk.com
The Power of Vaccines: ‘getting to zero’ for HIV and TB was an event hosted by the TB/HIV and Prevention Working Groups of the UK Consortium on AIDS and International Development. The meeting was sponsored by Pamela Nash MP and held on Friday, 18th May 2012, in Portcullis House, Westminster. Read more at http://storify.com/PamojaUK/the-power-of-vaccines
http://www.pamoja.uk.com
The Power of Vaccines: ‘getting to zero’ for HIV and TB was an event hosted by the TB/HIV and Prevention Working Groups of the UK Consortium on AIDS and International Development. The meeting was sponsored by Pamela Nash MP and held on Friday, 18th May 2012, in Portcullis House, Westminster. Read more at http://storify.com/PamojaUK/the-power-of-vaccines
http://www.pamoja.uk.com
The Power of Vaccines: ‘getting to zero’ for HIV and TB was an event hosted by the TB/HIV and Prevention Working Groups of the UK Consortium on AIDS and International Development. The meeting was sponsored by Pamela Nash MP and held on Friday, 18th May 2012, in Portcullis House, Westminster. Read more at http://storify.com/PamojaUK/the-power-of-vaccines
http://www.pamoja.uk.com
The Power of Vaccines: ‘getting to zero’ for HIV and TB was an event hosted by the TB/HIV and Prevention Working Groups of the UK Consortium on AIDS and International Development. The meeting was sponsored by Pamela Nash MP and held on Friday, 18th May 2012, in Portcullis House, Westminster. Read more at http://storify.com/PamojaUK/the-power-of-vaccines
http://www.pamoja.uk.com
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
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Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
1. Immune Monitoring in Vaccine Trials
Jill Gilmour
Exec Director IAVI HIL
Imperial College, London
Symposium on Innovations in Vaccine R+D
Wellcome Trust , London Sept 5th 2012
1
2. Immune Monitoring in Vaccine
Trials: Outline
1. Introduction and background
2. Context for immune monitoring on clinical trials
3. Available assays
4. Challenges
2
3. HIV Variability: The problem has a solution…….
A globally effective HIV vaccine will likely need to elicit:
• Broadly Neutralizing Antibodies: Prevent infection of any HIV strain
• Broadly Reactive T cells (CMI): Control Infection of any HIV strain
Neutralizing Abs
Cell Mediated
Immunity (CMI)
AIM to elicit both in a final product
Phase IIB testing of vaccine candidates that elicit either broad cellular or broadly neutralizing
antibodies will yield valuable information for field re-distinct immunological spaces.
3
4. An Introduction
The Human Immunology Laboratory (HIL)
Mission
Deliver high quality clinical trial data to prioritize and develop HIV
vaccine candidates for IAVI and the field
Coordinate and support IAVI’s global network of clinical
laboratories
Inform the next generation of HIV vaccine design and assessment
through translational clinical research on the African epidemic
4
5. IAVI R&D Network Global outlook
IAVI
Development
Design and IAVI Human
Development Lab Immunology Lab
IAVI NAC
at Scripps
Innovation Fund grants
IAVI India Lab
Immune
Neutralizing Vectors correlates/
Antibody Consortium LAC
Consortium
Clinical research
centers
IAVI collaborations with CAVD, HVTN, MVI and UK-HVC.
5
6. Immune Monitoring in Clinical Trials
Context
• Regulatory environment
– In EU member states, laboratories performing testing on clinical trial
samples should be accredited e.g. GCLP, and are subject to audit by
regulatory bodies
– Quality systems to ensure integrity of data
– Maybe a requirement to validate assays
• Standardization and method validation
– Need to pool data from multiple clinical centers and compare data
across products, regimens, sites etc
– Ensures studies are powered to meet primary objectives
• Go/ No-Go must be based on robust and scientifically sound data
6
7. Immune Monitoring in Clinical Trials
Context Cont’d
Stage of product development
• Phase I/II Trials:
– Primary assays: Accurately assess response rate, kinetics,
magnitude to optimize dose and regimen. Hypothesis testing.
– Research assays: Characterize immunogenicity and test/generate
additional hypothesis
• Efficacy Trials
– Primary assays similar to phase I/II with some additional validation
and streamlining
– Test a proportion of volunteers. Important for manufacturing e.g.
ensure potency between lots.
– Research assays to assess correlate or mechanism of efficacy.
– Implications for vaccine design and manufacturing e.g. optimizing
dose, monitoring vaccine potency as product released to market etc
7
8. Correlates of protection after vaccination;
defined quantitative measures. S. Plotkin, Clin
Inf Dis. 2008
For many vaccines we don’t know exact correlates of
protection; HIV, TB, Malaria
8
9. What have we learned from HIV vaccine efficacy
studies to date?
• Vaxgen gp 120 (No efficacy)
– Induced Env-specific non-neutralizing antibodies and tier 1 neuts
• STEP Merck Ad5 gag-pol-nef (No efficacy)
– Induced “poly-functional” CD8 T cells
– Limited CD8 breadth
– Evidence of protection against vaccine matched viral strains in vaccine recipients in vivo
and in vitro
• RV144 Canarypox + gp 120 (31% reduction of HIV-1 acquisition with no viral load effect)
– Induced Env-specific non-neutralizing antibodies and tier 1 neuts
– Predominantly CD4 Env-specific T cells
– Correlates analysis (V2 antibody binding)
• DNA prime + Ad5 boost: gag-pol-nef, env A, B and C
– Data expected 3-4Q 2013
– Induces “polyfunctional” T cells
– Antibody and CD4 env responses
9
10. Immunogenicity Go/No-go Criteria:
Cellular and Antibody
General Criteria (not product specific)
Modeling suggests a public health benefit with a 50% partially effective vaccine
Go > 60% response rate
Demonstrate superiority either qualitatively and quantitatively to candidates
which have been, or are in efficacy testing
PLUS
Product Specific Criteria-test rationale
Enhanced breadth, depth of coverage
o Evidence of coverage in developing world
Enhanced magnitude and quality of response
o Anti-viral activity, proliferation, CD4 and CD8, avidity, affinity, B cell memory
Induction of effective, boostable, memory response
Mucosal targeting
10
11. Outline
1. Introduction and background
2. Context for immune monitoring on clinical trials
3. Available assays
4. Challenges for the future
11
12. Primary and secondary assays in common use to
assess vaccine immunogenicity:
Cellular Antibody
Response rate ELISPOT ELISA
1o Kinetics Magnitude
Target antigens
Flow cytometry Antibody class / subclass
Phenotype CD8 CD4 Memory CD4 B Memory
2o
Function Viral Inhibition Assay Neutralisation Assay
Proliferation, Cytokines…… Non-neutralising: ADCC, ADCVI, V2
Breadth ELISPOT: Epitope mapping Epitope mapping
Viral Inhibition Assay Neutralization Assay
3o Location GI for containment of viral reservoir GI for containment of viral reservoir
(mucosal GU for containment of infection GU for containment of infection
sampling)
• Research assays: novel technologies e.g. Proteomics, genomics, DNA
microarrays, RNA-sequencing, single cell multiplexing e.g. fluidym, nano-string,
• Antibody gene sequencing 12
13. Example primary and secondary T cell immunogenicty
assessment for an Ad35 GRIN-Env vaccine regimen
IFN-g ELISPOT – Gag peptide pool >18 peptides mapped /
3000
2000
1000 Map Gag 8 unique regions in 8
SFC/106 PBMC
500
400
Epitopes individuals
300 1-3 epitopes / vaccinee
200
100
0
Low Mid High GRIN
Conserved vs variable epitopes
Log Inhib
Polychromatic Flow Cytometry
13
14. Limitations of Most T Cell Assays
High concentrations
High concentrations Indirect measurements
ofof exogenous peptide
synthetic antigen (peptide) (e.g. cytokines, peforins)
New methods of assessing CTL
function need to be developed Limited to
peripheral
blood
Irrelevant Targets Do not measure antiviral function
(B-cell lines) (MHC tetramer stain)
Adapted from Watkins 2008
15. Alternative Assay: Viral Inhibition Assay
High concentrations Indirect measurements
Whole HIV Direct Antiviral Effects
of synthetic antigen (peptide)
CD8
The Cell
The in vivo
Antigen New methods of assessing CTL
e.g. VIA Assess
mucosal
responses
The site
CD4
HIV infected
Autologous CD4
T Cells
XCD4
Measure antiviral activity
The outcome
The in vivo target
17. CD8 mediated inhibition of and HIV-1IIIB
correlates with in vivo virus control HIV-1
Spentzou et al (2010) JID 201: 720-729
17
18. In VIA Volunteers vaccinated with MRK-AD5 gag-pol-
nef inhibit only viruses matched to vaccine insert:
As predicted by efficacy data
Total vaccinees = 16. Efficient inhibition > 1.5 log10 inhibition.
18
19. VIA activity correlates with viral control in HIV
and vaccinated NHP controlling SIV challenge
■ 1st generation VIA correlates to in vivo virus control and excellent
specificity in HIV vaccine trials (Spentzou et al. JID. 2010)
■ Higher inhibition in the VIA correlates to lower viral loads in vivo. (Julg
et al. JVI 2010)
■ VIA inhibition correlates with viral load dynamics over time (CHAVI 001)
(Freel et al. JVI 2012)
■ VIA in DNA-Ad5 vaccinated NHP correlate with lowered peak and set
point viral loads (Yamamoto et al. J.Virol. 2012)
■ VIA like assay (ICS) results correlate with in vivo control (LTNP)
(Migueles et al. PLoS Path. 2011)
■ VIA in LN cells correlates with protection against live-attenuated SIV
(Picker et al. unpublished data) 19
20. Location, location, location. S. Plotkin, Clin Inf Dis. 2008
HIV – Mucosal sampling is critical
Over 50% of all T cells reside in the gut
The gut is the initial site of
High-level HIV replication
Massive CD4T cell depletion
--occurs within the first two weeks after infection
--observed after intravenous, intra-rectal, oral and
vaginal challenges
Limiting the initial viral replication in the gut could be crucial for
an AIDS vaccine
20
21. Mucosal Assay Development
• Assess the feasibility of various mucosal sampling
methods in clinical trial setting
• Develop clinical sampling methods and assays to assess
vaccine induced mucosal immune responses in UK and
Africa, focused on two assays
(a) cellular responses in the gut
(b) antibody responses in genital secretions
Apply into IAVI sponsored/collaborative clinical trials
21
22. CD8 T cell responses to gag in
blood compared with gut
Differences in phenotype and function between blood and gut,
and between colon and duodenum also observed
23. KAVI developing as a Centre of Excellence in
Mucosal Immunology in East Africa
Supported by and IAVI and HIL, KAVI has
embarked on a number of studies on
mucosal immunology:
- 2009 – initiated study to develop mucosal
sampling methods and assays to assess
mucosal immune responses in GU tract
- 2011 – initiated pilot study to assess
cellular responses in GALT (colon) using
IAVI-HIL methodologies
- 2011 – initiated mucosal sampling in
vaccine trials
Haas et al Nature 2010 Mar 11; 464(7286):
217-23
23
24. Mucosal Specimen Collection and Assay Methods
Sampling Method Assay
Merocel sponge
Antibody (Ab)
(rectal and cervical)
Digene cytobrush
MMC
(rectal and cervical)
Semen MMC and Ab
Rectal biopsies MMC
SoftCup MMC and Ab
Aspirator Ab
Saliva (active and passive) Ab
Oro and naso-pharyngeal swabs Ab 24
25. Other assays for assessment of T cells
For HIV – Makedonas & Betts 2010
TB, Malaria & other
diseases plethora of
possible responses
TCR avidity, affinity, clonotype
‘The degree of polyfunctionality of CD8+ T cells correlates
to the number of functions for which are assayed.’
Novel technologies: e.g. Proteomics, genomics, DNA/RNA microarrays,
RNA-sequencing, single cell multiplexing e.g. fluidigm, nano-string,
25
26. Gene expression profiles induced by YF-17D vaccination in
the European and Ugandan population
A. YF-17D vaccination induces different
gene expressions in Lausanne and
Entebbe. (A) Number of genes at 5% FDR
with a threshold of 2 or 3 fold change. The
magnitude of gene expression changes
was higher in Lausanne compared to
Entebbe. (B) Fold changes of the top 100
genes in Lausanne and Entebbe at 3, 7,
14, 56 and 84 days after a first
vaccination. The expression changes were
observed at days 3 and 7 after YF-17D
vaccination. The expression changes of
individuals genes was different in
VGTI (Rafick Sekaly), UVRI and IAVI Lausanne and Entebbe.
B.
27. Single Cell Genomics
Just like flow cytometry, this technology provides us with two
independent pieces of information:
– How many cells express a gene?
– How much do these cells express?
Standard (bulk) analysis confounds these two measurements to
generate an average
Single cell analysis allows us then to answer another question:
– What is the co-expression of genes?
Slide courtesy Mario Roederer and CAVD VIMC-T cell consortium
28. Fluidigm Technology
Dispense cDNA into Microfluidics
Sample cDNAChip
sample vessels
Primers & probes into
reagent vessels
Primers & Probes
Microfluidics mixes all
combinations in
nanoliter-sized
chambers
40 Cycle RT-PCR
Monitor fluorescence
from each chamber
28
29. Why is Single Cell Important?
BLIMP1
CD84 (SLAMF5) TNFR-1
BLIMP1
CD84 (SLAMF5) TNFR-1
Single cell analysis reveals a completely different picture of
regulation of these genes!
30. Fluidigm Analysis Summary
• On Single Cells:
– Distribution of gene expression
– Coordinate regulation of genes
– Reveals further heterogeneity (subsets) – potential correlates for
vaccine or disease analysis
• On Bulk Populations (~100 cells)
– Remarkable precision & sensitivity (RT-PCR)
– Economical, directed micro-array-like analysis
• Needs enormous bioinformatics support!
30
32. Assays to Monitor the Humoral Response
Research Assays
• B Cells
– B cell Elispot (memory B cells)
– B cell phenotyping
• Antibody
– Deep sequencing/moAb isolation to characterize engagement &
mutation of Ab genes.
– Isolation and characterization of Env-specific monoclonal
antibodies (IgG and IgA) from B memory cells and plasmablasts
sorted according to homing receptors in the systemic and
mucosal compartments
– Use antibodies to explore anti-viral functions e.g. aggregation,
inhibition of trancytosis, mucus inhibition
– Epitope mapping
32
33. Challenges
• Need a pipeline of immunogens for clinical testing
• Lack of human challenge models and efficacy trial and data
– E.g. Need to define what an effective broadly cross-
reactive antibody or anti-viral T cell response
• Bio-informatics and data management are not keeping up
with technology and data bases not tranlsational
• Define targets-functional or structural constraints
• Standardization and qualification in vaccine trials
33
34.
35. Developing Assays Defining Immunogenicity
Go/No-go Criteria
•Viral control is possible
•Effective immune responses
HIV •Target immunogens
Pathogenesis •Transmission
NHP •Host and viral genetics
Efficacy
• Protection is possible
•Optimize dose, regimen,
e.g. passive antibodies Clinical Trial
•Safety, experience with product
• Viral control possible Data
•Immunogenicity e.g response rate,
e.g. CMV, Live attenuated,
kinetics, function, breadth
Ad26/MVA mosaic,
•Test strategy e.g. Increased breadth,
DNA/IL12/Ep+Ad5
function, location
• Immune correlates
e.g. LAV-VIA in lymph-node,
CMV broad TEM, DNA+Ad5 VIA
Efficacy Trials Correlates of protection
Mechanism of protection
35
36. Assay Validation and Qualification
• Primary Immunogenicity Assays
– Validate and document fit for purpose
– Hypothesis testing
– Good precision, accuracy, rigorous and robust
– Ideally low cost and high throughput
– Critical as progress to large scale manufacturing
• Secondary
– Qualified
– Characterize immunogenicity, test secondary hypothesis, generate
new hypothesis
• Exploratory
– R+D
36
37. Immune Monitoring in Clinical Trials
Context Cont’d
• Data from the field
– e.g. Step trial and RV144
– Advancements in systems biology, deep sequencing, and other
technologies enable us to look at immune responses in exquisite
detail
• Post RV144 and STEP
– Tendency to assess every cellular and humoral immune response
possible –may not feasible for every trial
• Partnerships, collaborations, multiple clinical centers, study
populations and funders / sponsors required
– Complex operations, reporting, coordination, compromise,
37