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.
Oncolytic viruses (OVs) are therapeutically useful viruses which selectively infect and damage cancerous tissues without causing harm to normal tissues. Every virus has a specific cellular tropism that determines which tissues are preferentially infected, and what disease is caused. A number of naturally occurring viruses have a preferential, although non-exclusive, tropism for tumors and tumor cells. This probably has more to do with tumor biology than with virus biology as most tumors have evolved not only to avoid immune detection and destruction but also to resist apoptosis and translational suppression, which are the crucial responses used by normal cells to limit a virus infection. OVs can kill infected cancer cells in a number of different ways, ranging from direct virus-mediated cytotoxicity through various cytotoxic immune effector mechanisms.
Oncolytic viruses (OVs) is a group of viruses that selectively replicate in and kill cancer cells, while leaving the normal tissue uninfected. OVs provide a diverse platform for immunotherapy; they act as in situ vaccines, and can be armed with immuno-modulatory transgenes or combined with other immunotherapies, such as immune-checkpoint inhibitor, engineered T cell, bi-specific antibody or chemotherapies.
https://www.creative-biolabs.com/oncolytic-virus/oncolytic-virus-therapy-development.htm
Oncolytic viruses(OVs)are viral strains that can infect and kill malignant cells without harming normal cells, while simultaneously stimulate the immune system and creating system antitumor immunity. Oncolytic viruses have become one of the aglare immunotherapies that have been extensively studied and developed.
Creative Biolabs is a world-renowned service provider for immunotherapy. Taking advantage of the OncoVirapy™ platform, Creative Biolabs provides a comprehensive overview on the basic biology that support OVs as cancer therapeutic agents, including properties of inherent and engineered oncolytic viruses, mechanisms of viral targeting cancer cells, mechanisms of action of viruses killing cancer cells (induction of local and systemic anti-tumor immunity). Based on this basic knowledge review, we hope you can have a comprehensive understanding of OVs and quickly capture one of the frontiers of immunotherapy research.
Oncolytic viruses (OVs) are therapeutically useful viruses which selectively infect and damage cancerous tissues without causing harm to normal tissues. Every virus has a specific cellular tropism that determines which tissues are preferentially infected, and what disease is caused. A number of naturally occurring viruses have a preferential, although non-exclusive, tropism for tumors and tumor cells. This probably has more to do with tumor biology than with virus biology as most tumors have evolved not only to avoid immune detection and destruction but also to resist apoptosis and translational suppression, which are the crucial responses used by normal cells to limit a virus infection. OVs can kill infected cancer cells in a number of different ways, ranging from direct virus-mediated cytotoxicity through various cytotoxic immune effector mechanisms.
Oncolytic viruses (OVs) is a group of viruses that selectively replicate in and kill cancer cells, while leaving the normal tissue uninfected. OVs provide a diverse platform for immunotherapy; they act as in situ vaccines, and can be armed with immuno-modulatory transgenes or combined with other immunotherapies, such as immune-checkpoint inhibitor, engineered T cell, bi-specific antibody or chemotherapies.
https://www.creative-biolabs.com/oncolytic-virus/oncolytic-virus-therapy-development.htm
Oncolytic viruses(OVs)are viral strains that can infect and kill malignant cells without harming normal cells, while simultaneously stimulate the immune system and creating system antitumor immunity. Oncolytic viruses have become one of the aglare immunotherapies that have been extensively studied and developed.
Creative Biolabs is a world-renowned service provider for immunotherapy. Taking advantage of the OncoVirapy™ platform, Creative Biolabs provides a comprehensive overview on the basic biology that support OVs as cancer therapeutic agents, including properties of inherent and engineered oncolytic viruses, mechanisms of viral targeting cancer cells, mechanisms of action of viruses killing cancer cells (induction of local and systemic anti-tumor immunity). Based on this basic knowledge review, we hope you can have a comprehensive understanding of OVs and quickly capture one of the frontiers of immunotherapy research.
This PPT is about immune system and immune therapy, some basic knowledge about Chimeric Antigen Receptor or CAR technology and its application on tumor therapy.
chimeric antigen receptor, its structure and role in killing tumor cells,mechanism of antitumor killing, car's in clinic,evolution of cars and new chimeric antigen models
Therapeutic prospects in Cancer Immunotherapy.
Interleukins for Renal Cell Carcinoma.
BCG for Bladder Cancer.
Vaccination Strategies: Oncolytic virus for melanoma, Dendritic Cell therapy for CA Prostate.
Immune Checkpoint inhibitors. PD1 and PD L1 inhibitors.
Adoptive Cell Therpay. CAR T Cell Therapy
Clinical efficacy. Costs.
A detailed ppt about cancer immunotherapy.
includes:-
Immunosurveillance and Immunoediting
Dentritic cell vaccines
Antibody therapy
Combined therapy
immune blockades
Cytokine therapy
T cell therapy
Include latest research finding about therapy.
What is immunology?
What is Tumor?
Types of tumor
Classification of Malignant tumors
Malignant transformation of cells
General features of Tumor immunity
Tumor antigens
Tumor specific antigen
Tumor associated antigens
Immune response to tumor
Evasion of immune response by tumor
Cancer Immunosurveillance versus Immunoediting
Immunotechniques
RIA
ELISA
Viral Based Gene Delivery System for Car-t Cell Engineering Creative-Biolabs
A brief introduction about lentiviral vector gene delivery system and its application in CAR-T cell construction. Creative Biolabs offers high quality lentivirus based CAR gene delivery service to help with your CAR-T cell development projects.
Advances in Oncolytic Virotherapy - Creative BiolabsCreative-Biolabs
Oncolytic virotherapy, an innovative approach leverages the natural ability of viruses to infect and kill tumor cells, offering a beacon of hope for patients battling cancer. Our journey through this domain uncovers the mechanisms of action of oncolytic viruses, explores representative examples, discusses strategic modifications and combinations with other therapies, addresses challenges, and reviews the clinical status of this cutting-edge treatment.
This PPT is about immune system and immune therapy, some basic knowledge about Chimeric Antigen Receptor or CAR technology and its application on tumor therapy.
chimeric antigen receptor, its structure and role in killing tumor cells,mechanism of antitumor killing, car's in clinic,evolution of cars and new chimeric antigen models
Therapeutic prospects in Cancer Immunotherapy.
Interleukins for Renal Cell Carcinoma.
BCG for Bladder Cancer.
Vaccination Strategies: Oncolytic virus for melanoma, Dendritic Cell therapy for CA Prostate.
Immune Checkpoint inhibitors. PD1 and PD L1 inhibitors.
Adoptive Cell Therpay. CAR T Cell Therapy
Clinical efficacy. Costs.
A detailed ppt about cancer immunotherapy.
includes:-
Immunosurveillance and Immunoediting
Dentritic cell vaccines
Antibody therapy
Combined therapy
immune blockades
Cytokine therapy
T cell therapy
Include latest research finding about therapy.
What is immunology?
What is Tumor?
Types of tumor
Classification of Malignant tumors
Malignant transformation of cells
General features of Tumor immunity
Tumor antigens
Tumor specific antigen
Tumor associated antigens
Immune response to tumor
Evasion of immune response by tumor
Cancer Immunosurveillance versus Immunoediting
Immunotechniques
RIA
ELISA
Viral Based Gene Delivery System for Car-t Cell Engineering Creative-Biolabs
A brief introduction about lentiviral vector gene delivery system and its application in CAR-T cell construction. Creative Biolabs offers high quality lentivirus based CAR gene delivery service to help with your CAR-T cell development projects.
Advances in Oncolytic Virotherapy - Creative BiolabsCreative-Biolabs
Oncolytic virotherapy, an innovative approach leverages the natural ability of viruses to infect and kill tumor cells, offering a beacon of hope for patients battling cancer. Our journey through this domain uncovers the mechanisms of action of oncolytic viruses, explores representative examples, discusses strategic modifications and combinations with other therapies, addresses challenges, and reviews the clinical status of this cutting-edge treatment.
Learn more about how AARSOTA Bio-Immunotherapy integrates with Hope4Cancer's non-toxic cancer treatment strategies. Hope4Cancer's alternative cancer treatments reduces the toxic effects of prior chemo and radiation treatments while directly healing the cancer.
Oncolytic viruses (OVs) are therapeutically useful viruses which selectively infect and damage cancerous tissues without causing harm to normal tissues. OVs can kill infected cancer cells in a number of different ways, ranging from direct virus-mediated cytotoxicity through various cytotoxic immune effector mechanisms.
https://www.creative-biogene.com/products/oncolytic-virus.html
Global cancer immunotherapy market outlook 2020KuicK Research
"Global Cancer Immunotherapy Market Outlook 2020" Report Highlight:
Introduction & Classification of Cancer Immunotherapy
Global Cancer Immunotherapy Pipeline by Company, Indication & Phase
Marketed Cancer Immunotherapies Clinical Insight & Patent Analysis by Company & Indication
Global Cancer Immunotherapy Pipeline: 1834 Drugs
Marketed Cancer Immunotherapies: 113 Drugs
Cancer Monoclonal Antibodies Pipeline: 622 Cancer mAb
Cancer Vaccines Pipeline: 312 Vaccines
Marketed Cancer mAb: 36 mAb
Marketed Cancer Vaccines: 12 Vaccines
Download Global cancer immunotherapy market outlook 2020KuicK Research
\"Global Cancer Immunotherapy Market Outlook 2020\" Report Highlight:
Introduction & Classification of Cancer Immunotherapy
Global Cancer Immunotherapy Pipeline by Company, Indication & Phase
Marketed Cancer Immunotherapies Clinical Insight & Patent Analysis by Company & Indication
Global Cancer Immunotherapy Pipeline: 1834 Drugs
Marketed Cancer Immunotherapies: 113 Drugs
Cancer Monoclonal Antibodies Pipeline: 622 Cancer mAb
Cancer Vaccines Pipeline: 312 Vaccines
Marketed Cancer mAb: 36 mAb
Marketed Cancer Vaccines: 12 Vaccines
Global cancer immunotherapy market outlook 2020KuicK Research
"Global Cancer Immunotherapy Market Outlook 2020" Report Highlight:
Introduction & Classification of Cancer Immunotherapy
Global Cancer Immunotherapy Pipeline by Company, Indication & Phase
Marketed Cancer Immunotherapies Clinical Insight & Patent Analysis by Company & Indication
Global Cancer Immunotherapy Pipeline: 1834 Drugs
Marketed Cancer Immunotherapies: 113 Drugs
Cancer Monoclonal Antibodies Pipeline: 622 Cancer mAb
Cancer Vaccines Pipeline: 312 Vaccines
Marketed Cancer mAb: 36 mAb
Marketed Cancer Vaccines: 12 Vaccines
Oncolytic viruses (OVs) is a group of viruses that selectively replicate in and kill cancer cells, while leaving the normal tissue uninfected. OVs provide a diverse platform for immunotherapy; they act as in situ vaccines, and can be armed with immuno-modulatory transgenes or combined with other immunotherapies, such as immune-checkpoint inhibitor.
https://www.creative-biolabs.com/oncolytic-virus/introduction-and-mechanism-of-oncolytic-virus-therapy.htm
The strategy implementation of immunotherapeutic for the treatment of cancer has gained prominence over the past decade. Oncolytic viruses (OVs) are viral strains that can infect and kill malignant cells without harming normal cells, while simultaneously stimulating the immune system and creating antitumor immunity.
https://www.creative-biolabs.com/oncolytic-virus/oncolytic-virotherapy-development-for-combination-therapy-with-cancer-immunotherapy.htm
Creative Biolabs provides a broad range of oncolytic virus engineering scope including Adenovirus, Herpes Simplex Virus, Measles Virus, Vaccinia Virus, etc.
https://www.creative-biolabs.com/oncolytic-virus/oncolytic-virus-construction.htm
Oncolytic virus immunotherapy knowledgeCandy Swift
Due to the in-depth knowledge of immunology and tumor biology, scientists of Creative Biolabs keep devoting endless effort to the development of immunotherapy strategies and reagents aiming at specific categories and features of various cancers.
https://www.creative-biolabs.com/oncolytic-virus/disease-specific-oncolytic-virotherapy-development.htm
Oncolytic virus immunotherapy is a therapeutic approach to cancer treatment that utilizes native or genetically modified viruses that selectively replicate within tumor cells.
https://www.creative-biolabs.com/oncolytic-virus/
Oncolytic viruses (OVs) provide a diverse platform for immunotherapy; they act as in situ vaccines, and can be armed with immuno-modulatory transgenes or combined with other immunotherapie. Taking advantage of the OncoVirapy™ platform, Creative Biolabs provides high-quality oncolytic virus therapy development services for clients globally.
https://www.creative-biolabs.com/oncolytic-virus/oncolytic-virotherapy-development-for-combination-therapy-with-cancer-immunotherapy.htm
Oncolytic viruses (OVs) is a group of viruses that selectively replicate in and kill cancer cells, while leaving the normal tissue uninfected. In addition to direct oncolysis activity, OVs are also very effective at inducing immune responses against tumor cells.
https://www.creative-biolabs.com/oncolytic-virus/
Ready-to-use Pre-Made Oncolytic Virus Product.pdfCandy Swift
Creative Biolabs has built a state-of-the-art oncolytic virus engineering platform which provides a series of purified pre-made oncolytic virus for reporter-encoding, cytokine-expressing, immune checkpoint antibody-arming, capsid-modifing and miRNA-expression.
https://www.creative-biolabs.com/oncolytic-virus/pre-made-oncolytic-virus.htm
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Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
Professional air quality monitoring systems provide immediate, on-site data for analysis, compliance, and decision-making.
Monitor common gases, weather parameters, particulates.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
A brief information about the SCOP protein database used in bioinformatics.
The Structural Classification of Proteins (SCOP) database is a comprehensive and authoritative resource for the structural and evolutionary relationships of proteins. It provides a detailed and curated classification of protein structures, grouping them into families, superfamilies, and folds based on their structural and sequence similarities.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
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The ambient solar wind that flls the heliosphere originates from multiple
sources in the solar corona and is highly structured. It is often described
as high-speed, relatively homogeneous, plasma streams from coronal
holes and slow-speed, highly variable, streams whose source regions are
under debate. A key goal of ESA/NASA’s Solar Orbiter mission is to identify
solar wind sources and understand what drives the complexity seen in the
heliosphere. By combining magnetic feld modelling and spectroscopic
techniques with high-resolution observations and measurements, we show
that the solar wind variability detected in situ by Solar Orbiter in March
2022 is driven by spatio-temporal changes in the magnetic connectivity to
multiple sources in the solar atmosphere. The magnetic feld footpoints
connected to the spacecraft moved from the boundaries of a coronal hole
to one active region (12961) and then across to another region (12957). This
is refected in the in situ measurements, which show the transition from fast
to highly Alfvénic then to slow solar wind that is disrupted by the arrival of
a coronal mass ejection. Our results describe solar wind variability at 0.5 au
but are applicable to near-Earth observatories.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...
Oncolytic Virus Therapy Development - Creative Biolabs
1. 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.
ONCOLYTIC VIRUS
THERAPY DEVELOPMENT
2. About
Creative Biolabs
The Best
Solutions
for Immunotherapy
Since our inception in 2004, our research and service capacity has
expanded to the entire new drug discovery and development pipeline,
including early discovery, preclinical testing, process development, cGMP
manufacturing, phase I-III clinical trails. As a global company, we have
more than 200 talented and well-trained scientists located in different
continents working closely with partners from the entire world to develop
and produce medicines of tomorrow. Facing the increasing challenges
from cancer treatment, our scientists establish systematic immunotherapy
development platforms to meet the need of our customers worldwide.
Our featured platforms include CellRapeutics™ for TCR and CAR
development, and OncoVirapy™ for oncolytic virus development.
3. ONCOLYTIC
VIROTHERAPY
Oncolytic Virus
Oncolytic viruses represent a new class
of therapeutic agents that promote anti-
tumor responses through a dual
mechanism of action that is dependent on
selective tumor cell killing and the
induction of systemic
anti-tumor immunity.
4. In vivo validation studies services for engineered oncolytic virus.
include but not limited to construction of xenograft/syngeneic
animal models, immunogenicity tests, biodistribution/PK tests,
efficacy, and toxicology studies
OncoVirapy™
Platform
Taking advantage of the OncoVirapy™
platform, Creative Biolabs provides
customized, standardized, and reliable
and high-quality oncolytic virus therapy
development services for clients
globally. Various types of oncolytic
viruses engineering systems have
been established in-house to facilitate
oncolytic virus development with less
time and reduced budget. GMP-
compliant manufacture of oncolytic
virus is also included in
our services.
Diverse engineering methods to make full use
of natural properties of various viruses, and
already developed therapeutic methods.
A variety of prove-of-concept in vitro assays
service for engineered oncolytic virus to test the
virus functional activity.
oncolytic virotherapy develp[ment service for various
type of tumor, including melanoma, genitourinary
malignancies, hepatocellular carcinoma, breast
cancer etc.
5. Oncolytic Virotherapy Development Process
Basic Cancer
Biology Study
Abnormal signaling
pathway study
Target identification
Malignant cell type
Tissue specificity
Oncolytic Virus
Vector Construction
Virus species
In vitro Validation
Replication Capacity
In vivo Validation
Non-tumor bearing
animal model
Pharmacology
Virus tropism
Tissue selectivity
Therapeutic
Strategy
Monotherapy
Combination
therapay
Arming with
therapeutic gene
Safety issue
Delivery Expression of
transgene
Function of transgene
Tumor cell selectivity
Tumor lysis capacity
Genetic stability
Infectivity
Tumor-bearing
xenograft/syngeneic
animal model
Biodistribution
Toxicology, safety
www.creative-biolabs.com
Antitumor response
6. Basic Study
Cancer Biology
Cancer is a group of diseases involving
abnormal cell growth with the potential to
invade or spread to other parts of the body.
To our knowledge, both immunologic and
cancer biologic approaches have to be
combined to enhance the efficacy of
anticancer therapy, and this will always be
a challenge for the next generation of
cancer immunotherapy. Only on the basis
of molecular mechanisms and other
proved evidence that underline the
pathogenesis of specific type of cancer,
can a better therapeutic strategy be
developed.
7. Immunotherapy in cancer is rapidly
evolving, with various treatments
being investigated for their potential
to provide long-term survival across
a broad range of tumor types, and
for their synergistic activity when
combined with other treatment
modalities. It is important now to
determine how to advance
this field and the way to use
these new immunotherapies
most effectively to achieve
the best patient outcomes.
Therapeutic Strategy
Reversing the inhibition of adaptive immunity (blocking T cell
checkpoint pathways)
CTLA-4 inhibition, PD-1/PD-L1 inhibition, LAG-3 inhibition, TIM-3 inhibition
Switching on adaptive immunity (promoting T cell co-stimulatory receptor
signaling using agonist antibodies)
Enhancing OX40 signaling, Enhancing CD27 signaling, CD40 activation,
Promoting CD137 signaling
Expanding adaptive immunity
Adoptive cell therapy
Improving the function of innate immune cells
Stimulating dendritic cell, Manipulating NK-cell inhibitory receptors
Activating the immune system (potentiating immune-cell effector
function)
Oncolytic virus, Therapeutic vaccines
8. Oncolytic Virus Vector Construction
Viruses used as oncolytic vector
Nucleic acid
Capsid
symmetry
Envelope Family Virus Cell receptor
DNA
Icosahedral
Naked Adenoviridae Adenovirus CAR
Enveloped Herpesviridae HSV-1
HVEM/nectin 1/
nectin 2
Complex Enveloped Poxviridae Vaccina virus Unknow
RNA
Icosahedral Naked
Reoviridae Reovirus Unknow
Picornaviridae Poliovirus
CAR/ICAM-1/DA
F
Helical Enveloped
Rhabdoviridae VSV LDLR
Paramxyoviridae Measles virus SLAM/CD46
9. Oncolytic Virus Vector Construction
As we move in the direction of intentionally using virus infections to mediate tumor destruction, it is apparent that a targeted
virus with exquisite tumor specificity will be superior to its non-targeted counterpart, allowing for the administration of higher
tumor destructive doses without toxicity to normal tissues. Cancer cells distinguish themselves from their normal counterparts
by alterations in cell physiology such as self sufficiency in growth signals, insensitivity to growth inhibition signals, evasion of
apoptosis, limitless replication potential, sustained angiogenesis and tissue invasion and metastasis. These alterations make
these a generous host for viruses and hence these properties can be utilized for selective replication of oncolytic viruses in
cancer cells.
Targeting Virus Tropism
Natural tropism
Deletion of viral
genes required
for virus
replication in
normal cells
Engineered
with protease
target
sequence
Ablation of
unwanted
tropism
(MicroRNA
targeting)
Engineered
with
tissue/tumor
specific
promoter
Using cellular
vehicle
Designing strategy of modification of oncolytic virus tropism
10. Oncolytic Virus Vector Construction
Basically oncolytic virus exert antitumor activity by direct lysis of cancer cell and activation of immune system. Although
OVs can extensively transfect and kill tumor cell, a percentage of tumor cell remains uninfected. Bystander killing can be
achieved, both locally at the site of a spreading infection and systemically at uninfected tumor sites, by genetically arming
the virus using one of several possible approaches.
Arming strategy
Immune-stimulatory
cytokines & receptors
Immune checkpoint
inhibitors
T cell Bispecific
Antibody
Prodrug
convertases
Short hairpin RNA
11. Oncolytic Virus Vector Construction Safety
Unwanted normal tissue pathology
Studies of the mutation rates of viral polymerases, the generation
of quasispecies, the evolution of viral populations and the
evolution between dominant subspecies within a virus population
are therefore of great interest and relevance to the OV field.
It is important that precautions for infectious
material and biological safety, and biosafety
guidelines be followed when administering
oncolytic virus. Hence, the issue of safety
worth being handled in advance, even at the
stage of oncolytic vector construction.
Careful steps must be taken to avoid the
creation of OVs that might evolve to become
serious pathogens. For the problem of
undesirable transmission, contingency plans
to terminate the spread and/or transmission
of an infection can increase clinical
confidence in viral therapy.
Unwanted transmission
The consequences of transmission to others might not be well
understood and precautions should be taken to minimize
exposure of healthcare providers, family members and other
patient contacts. Non-clinical viral shedding studies can be useful
in preparing for clinical studies and evaluating detection methods
Toxicity
The toxicology assessment of an oncolytic virus should be
comprehensive enough to identify, characterize and quantify
potential local and systemic toxicities following administration.
12. Validation of
Oncolytic vector
Plaque purification
assay
Identity assay
Replication assay
Tumor lytic assay
Transgene
expression assay
Transgene
functional assay
Immunogenicity
Test
Efficacy Study Toxicology Study
Biodistribution/PK
Test
In vivoIn vitro
13. Considerations
in Validation
Evaluation of Selectivity
For in vitro validation studies, prior to using animal models, experiments conducted to
characterize selectivity in normal and tumor cells should address selective gene expression,
cytotoxicity and viral replication. To this end, candidate oncolytic viruses should be assayed
in vitro for lysis and/or replication on tumor/permissive or nonpermissive cell lines.
14. Considerations
in Validation
Function of Transgene
If the oncolytic virus contains a transgene, it is important that the animal species be
pharmacologically responsive to the expressed protein. If the expressed transgene is inactive in
the animal species, oncolytic virus can be engineered to express the analogous species-specific
transgene and used in non-clinical studies to assess both activity and safety.
15. Considerations
in Validation
Selection of animal model
Selection of the animal model should take into consideration the purpose of the study as well
as the viral tropism, infectivity, replication ability, cytopathic potential and anti-tumor effect of
the oncolytic virus.
Ideally, a xenograft or syngeneic model should
represent the tumor biology and pathology of the
target clinical population to the clinical outcome.
Non-tumor-bearing, can be
used to evaluate the safety
of the OV.
16. Considerations
in Validation
Pharmacology & Biodistribution
Biodistribution studies in animals
address oncolytic virus dissemination
to target and non-target organs. OV
dissemination can be detected using an
assay for nucleic acid sequence. Also,
sensitive assays such as quantitative
polymerase chain reaction (QPCR) can
be applied to test the presence of
oncolytic virus sequences in animal
organs and tissues
It is critical to assess the bioactivity and
pharmacologic profile of the oncolytic
virus to understand the ability of the OV
to induce the desirable anti-tumor effect.
The experiments designed should help
to define a pharmacologically active
dose range, with establishment of an
optimal dose and a minimally effective
dose, and also to determine a
potentially optimal route for virus
product administration.
17. Featured Products
By the OncovirapyTM platform, Creative Biolabs is now able to provide
products of various oncolytic virus vector for our customers globally. To be
specific, our oncolytic vectors are designed on the basis of human adenovirus,
which has been widely used as a viral vector for gene therapy studies.
Moreover, most of the oncolytic adenovirus designed and produced with
arming of different kinds of transgene, such as for antibody, bispecific
antibody, immune modulator, miRNA and tumor-associated antigen. We
believe that our designed ready-to-build oncolytic vectors will facilitate the
research in cancer immunotherapy for scientists all over the world.
ITR E1A E1B pIX L1 L2 L3 L4 E3 L5 ITR
E2B E2A E4
18. Summary of oncolytic virus development
on OncoVirapy™ Platform
A. Basic cancer biology research
Cancer Type Malignant Cell Type
Abnormal signaling
pathway
B. Oncoytic Virus Vector Design
Tissue
selectivity
Virus
Species
Natural/Modified
Tropism
Therapeutic Gene
Arming
Safety issue
Neutralization issue
C. Therapeutic Strategy
Development
Monotherapy
Combination Therapy
D. Validation Studies
Replication
Capacity
Tumor Lysis
Capacity
Tumor cell
selectivity
Function of
Transgene
Selection and Construction
of Animal model
Pharmacology Biodistribution
Toxicology Safety
Antitumor/Host immunity Response
In vitro
In vivo
E. Oncolytic virus
Manufacture
19. The Best Solutions
for Immunotherapy
from Creative Biolabs
45-1 Ramsey Road
Shirley, NY 11967, USA
Tel: 1-631-871-5806
Fax: 1-631-207-8356
Email: inquiry@creative-biolabs.com