In this webinar:
Dr. Michele Ardolino, Assistant Professor at the University of Ottawa, Department of Biochemistry, Microbiology, and Immunology and Scientist Ottawa Hospital Research Institute, discusses: The body has a phenomenal weapon to fight infections and cancer: the immune system. This seminar focuses on how the immune system recognizes and shapes cancer and on how research in tumor immunology led to the development of life-saving and revolutionizing immuno-therapies.
The webinar is followed by a question & answer session.
View the video:
https://youtu.be/-a7DfHT8dU8
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n overview of current immunotherapy therapies used to treat cancer. Also provides MOA of various medications, and updates on SITC guidelines for metastatice melanoma.
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.
In this webinar:
Dr. Michele Ardolino, Assistant Professor at the University of Ottawa, Department of Biochemistry, Microbiology, and Immunology and Scientist Ottawa Hospital Research Institute, discusses: The body has a phenomenal weapon to fight infections and cancer: the immune system. This seminar focuses on how the immune system recognizes and shapes cancer and on how research in tumor immunology led to the development of life-saving and revolutionizing immuno-therapies.
The webinar is followed by a question & answer session.
View the video:
https://youtu.be/-a7DfHT8dU8
To learn more about CCSN, visit us at survivornet.ca
Follow CCSN on social media:
Twitter - https://twitter.com/survivornetca
Facebook - https://www.facebook.com/CanadianSurv...
Instagram: https://www.instagram.com/survivornet...
Pinterest - https://www.pinterest.com/survivornet...
n overview of current immunotherapy therapies used to treat cancer. Also provides MOA of various medications, and updates on SITC guidelines for metastatice melanoma.
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.
this slide contain information about antibody mediated anti-cancer therapy like antibody drug conjugates (ADC), Bispecific monoclonal antibody, Immuno-checkpoint therapy, biomarkers, mechanism of action of all 3 therapies, approved drugs of each category
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.
This presentation is part of MIU CE Pharmacy Program and is designed primarily for pharmacists with the following learning objectives:
1- Explain the mechanisms of action behind immune response to cancer and the application of immunotherapy in cancer treatment
2- Distinguish new and emerging immunotherapy classes and individual agents efficacy, safety to therapy in cancer treatment
3-Strategies to counsel and assist patients to overcome barriers to therapy, including Treatment side effects to improve adherence to therapy
CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein.
This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.
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
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.
CAR T-cell Therapy_A New Era in Cancer ImmunotherapyTuhin Samanta
Illusory Antigen Receptor (CAR) T-cell treatment includes hereditary alteration of patient's autologous T-cells to express a CAR explicit for a tumor antigen, following by ex vivo cell extension and re-imbuement back to the patient. Vehicles are combination proteins of a chose single-chain section variable from a particular monoclonal immune response and at least one T-cell receptor intracellular flagging spaces. This T-cell hereditary change may happen either by means of viral-based quality exchange strategies or nonviral techniques, for example, DNA-based transposons, CRISPR/Cas9 innovation or direct exchange of in vitro deciphered mRNA by electroporation.
Types of immunotherapy
Oncology
cancer vaccines
adoptive T cell transfer
oncolytic viruses
monoclonal antibodies
cytokine
treatment of cancer with immunotherapy
A type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is being studied in the treatment of some types of cancer. Also called chimeric antigen receptor T-cell therapy.
ROLE OF IMMUNE CELLS IN CANCER AND TARGETING IMMUNE CELLS FOR CANCER THERAPYSIVASWAROOP YARASI
Cancer immunotherapy is a therapy used to treat cancer patients that involves or uses components of the immune system. Some cancer immunotherapies consist of antibodies that bind to, and inhibit the function of, proteins expressed by cancer cells. Other cancer immunotherapies include vaccines and T cell infusions.
this slide contain information about antibody mediated anti-cancer therapy like antibody drug conjugates (ADC), Bispecific monoclonal antibody, Immuno-checkpoint therapy, biomarkers, mechanism of action of all 3 therapies, approved drugs of each category
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.
This presentation is part of MIU CE Pharmacy Program and is designed primarily for pharmacists with the following learning objectives:
1- Explain the mechanisms of action behind immune response to cancer and the application of immunotherapy in cancer treatment
2- Distinguish new and emerging immunotherapy classes and individual agents efficacy, safety to therapy in cancer treatment
3-Strategies to counsel and assist patients to overcome barriers to therapy, including Treatment side effects to improve adherence to therapy
CAR-T cells (Chimeric Antigen Receptor- T cells) are T cells that have been genetically engineered to produce an artificial T cell receptor for use in immunotherapy. Chimeric antigen receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific protein.
This therapy use to treat several type of cancer but significantly treat leukemia. And this therapy is very effective than other.
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
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.
CAR T-cell Therapy_A New Era in Cancer ImmunotherapyTuhin Samanta
Illusory Antigen Receptor (CAR) T-cell treatment includes hereditary alteration of patient's autologous T-cells to express a CAR explicit for a tumor antigen, following by ex vivo cell extension and re-imbuement back to the patient. Vehicles are combination proteins of a chose single-chain section variable from a particular monoclonal immune response and at least one T-cell receptor intracellular flagging spaces. This T-cell hereditary change may happen either by means of viral-based quality exchange strategies or nonviral techniques, for example, DNA-based transposons, CRISPR/Cas9 innovation or direct exchange of in vitro deciphered mRNA by electroporation.
Types of immunotherapy
Oncology
cancer vaccines
adoptive T cell transfer
oncolytic viruses
monoclonal antibodies
cytokine
treatment of cancer with immunotherapy
A type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein on the patient’s cancer cells is added in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion. CAR T-cell therapy is being studied in the treatment of some types of cancer. Also called chimeric antigen receptor T-cell therapy.
ROLE OF IMMUNE CELLS IN CANCER AND TARGETING IMMUNE CELLS FOR CANCER THERAPYSIVASWAROOP YARASI
Cancer immunotherapy is a therapy used to treat cancer patients that involves or uses components of the immune system. Some cancer immunotherapies consist of antibodies that bind to, and inhibit the function of, proteins expressed by cancer cells. Other cancer immunotherapies include vaccines and T cell infusions.
Pediatric patients are often faced with resistant or recurrent cancers that cannot be cured by chemotherapy, radiation, or surgery.
Immunotherapies have become viable therapeutic options for many cancer patients.
Some of these new pharmacologic medications are changing the landscape of treatment for pediatric cancers, while the utility of others is not yet known.
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Types of tumor antigens recognized by T cells
Immune mechanisms of tumor rejection
How tumors evade immune responses?
Novel therapeutic approaches (immunotherapies)
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.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
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New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
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.
2. Introduction
• The term cancer refers to a disease of cells
that show uncontrolled proliferation,
dedifferentiation(anaplasia), invasiveness and
the ability to metastasise (spread to distal
parts of body).
• Traditional therapies for cancer targets the
tumour and include – Surgery, radiation,
chemotherapy and targeted therapy.
3. Cancer Statistics in India
• Estimated number of people living with the disease:
around 2.25 million
• Every year, new cancer patients registered: Over
11,57,294 lakh
• Cancer-related deaths: 7,84,821
• Risk of developing cancer before the age of 75 years
-Male: 9.81%
-Female: 9.42%
• Cancers of oral cavity and lungs account for over 25%
of cancer deaths in males and cancer of breast and
oral cavity account for 25% cancers in females.
4. Immunotherapy for cancer
• Immunotherapy represents conceptually a
unique way of dealing with cancer which is to
focus on eliminating cancer indirectly by
harnessing the power of the host’s immune
system.
• The 2018 Nobel Prize in Physiology or
Medicine has been awarded jointly to two
cancer immunotherapy researchers, James P.
Allison, and Dr. Tasuku Honjo.
5. • Allison and Honjo were honored for their work on
uncovering ways to activate the immune system
to attack cancer, a breakthrough in developing
new cancer treatments.
• The discoveries of Honjo and Allison led to the
development of several drugs which allow for the
routine use of effective immunotherapy.
• Allison studied the T cell protein CTLA-4 and
Honjo discovered PD-1, which is another protein
found on the surface of some T cells. .
6. Mechanisms of cancer immune
evasion
• downregulation of antigen processing and
presentation machinery and thus antigen
presentation
• upregulation of PD-L1 on tumor cells and PD-1 on
effector T cells and facilitation of binding of PD-L1
and B7-1/2 to PD-1 and CTLA-4, respectively
• secretion of immune suppressive modulators
(TGF-β, IL-8, IL-10, IL-18, CSF1, VEGF, gangliosides,
ROS, Kynurenines, K+) and metabolites
(adenosine, PGE, lactate) into TME
7. • deprivation of immune activating metabolites
(glucose, arginine, glutamine, tryptophan)
from TME
• recruitment and/or activation of immune
suppressive cell populations e.g. Treg, myeloid
derived suppressor cells (MDSC), and tumor-
associated macrophages (TAM)
• inhibition of effector T cell infiltration
8.
9. Immunotherapeutic Approaches
• Immune checkpoint inhibition
• Vaccination
• Nonspecific stimulation of T cells
• Adoptive T Cell Transfer
• Bispecific Antibodies
10. Immune Checkpoint Inhibitors
• Inhibitors of Cytotoxic T Lymphocyte–
Associated Protein 4 (CTLA4)
• Inhibitors of Programmed Cell Death 1 (PD-1)
• Antagonists of PD-1 Ligand 1
• Combination of Anti–PD-1 and Anti–CTLA4
13. Inhibitors of Cytotoxic T Lymphocyte–
Associated Protein 4 (CTLA4)
blocks the interaction of CTLA-4 with B7 ligands
on APCs and thereby augments T-cell activation.
Ipilimumab
• Approved in 2011 for Unresectable metastatic
melanoma
• Approved in 2015 for Adjuvant therapy with
Stage III melanoma
• Approved in 2017 for Pediatric melanoma
Tremelimumab
14. Inhibitors of Programmed Cell Death 1
(PD-1)
blocks the interaction between PD-1 and its ligands.
Nivolumab
• Approved in 2014 for Unresectable or metastatic
melanoma with progression after ipilimumab therapy
• Approved in 2015 for NSCLC with progression after or
on platinum therapy & Metastatic RCC after prior anti-
angiogenic therapy
• Approved in 2016 for Hodgkin lymphoma & Head and
neck squamous cell carcinoma
• Approved in 2017 for Urothelial carcinoma, metastatic
colorectal cancer & Hepato cellular carcinoma
15. Pembrolizumab
• Approved in 2014 for Advanced or unresectable
melanoma
• Approved in 2015 for Metastatic NSCLC with PDL-
1 expression and progression on or after
platinum therapy
• Approved in 2016 for Recurrent SCCHN
• Approved in 2017 for Hodgkin lymphoma,
Urothelial carcinoma, Gastric & gastroesophageal
carcinoma
16. Antagonists of PD-1 Ligand 1
blocks the interaction of PD-L1 with PD-1
Atezolimumab
• Approved in 2015 for NSCLC with progression after or on
platinum therapy
• Approved in 2016 for Urolthelial carcinoma with
progression on or after platinum therapy
Durvalumab
• Approved in 2017 for Urothelial carcinoma
• Approved in 2018 for Non–small cell lung cancer
Avelumab
• Approved in 2017 for Urothelial carcinoma & Merkel cell
carcinoma
17. Combination of Anti–CTLA4 and Anti–
PD-1
Ipilimumab + nivolumab
• Approved in 2015 for Melanoma
• Approved in 2018 for Renal cell carcinoma
18. Therapeutic cancer vaccines
• vaccination with a known antigen (to generate
T cells that recognize cells expressing the
antigen)
• Sipuleucel-T
• T-Vec
19. Sipuleucel-T
• In 2010, the FDA approved the first-in-class
cancer treatment vaccine, sipuleucel-T
(Provenge®, manufactured by Dendreon),
• for treatment of hormone-refractory prostate
cancer and metastatic prostate cancer.
• It is designed to trigger an immune response to
prostatic acid phosphatase (PAP), an over-
expressed tumor antigen.
• Provenge is generated by isolating APCs and
cultured with a PAP linked to GM-CSF.
20.
21. T-Vec
• T-VEC (talimogene laherparepvec) was approved
by the FDA in 2015 for the local treatment of
unresectable cutaneous and nodal lesions in
patients with melanoma.
• T-VEC is an oncolytic herpesvirus that replicates
within tumors and expresses GM-CSF.
• Tumor antigens are released after virally induced
cell death, and the presence of GM-CSF can
promote an antitumor immune response.
22. • In T-VEC, the HSV-1 genome has been modified by
deletions of 2 copies of the RL1 gene, which encode a
neurovirulence factor, infected cell protein 34.5
(ICP34.5).
• In healthy cells, ICP34.5 is required for viral
proliferation. In cancer cells, however, HSV-1
proliferation does not require ICP34.5.
• Thus, deletion of ICP34.5 prevents viral proliferation
within healthy cells, but renders cancer cells
susceptible.
• This deletion of ICP34.5 makes the virus less
pathogenic, limiting HSV infection of noncancerous
cells, and providing for tumor-selective replication.
23. Inside a healthy cell, the virus
( ) is unable to replicate,
leaving the cell unharmed.
Inside a cancer cell, the virus
replicates and secretes GM-CSF
( ) until the cells lyses,
releasing more viruses, GM-CSF
and antigens ( ).
GM-CSF attracts dendritic cells to the
site, which process and present the
antigens to T cells. The T cells are
now “programmed” to identify and
destroy cancer cells throughout the
body.
T cells destroy
cancer cells
throughout the
body, including
those not directly
injected with the
virus.
Talimogene Laherparepvec: Proposed Mechanism of
Action for Systemic Immunologic Effect
24. Nonspecific stimulation of T cells
Interleukin 2 (as recombinant IL-2, aldesleukin)
• Interleukin 2 stimulates the proliferation of
activated T cells and the secretion of cytokines
from NK cells and monocytes. IL-2 stimulation
increases cytotoxic killing by T cells and NK cells.
• Aldesleukin is approved for use in patients with
metastatic renal cell cancer and metastatic
melanoma.
25. Adoptive T Cell Transfer
• Tumor-Infiltrating Lymphocytes (TILs)
• TCR-Transduced T Cells
• Chimeric Antigen Receptor T Cells (CAR T
Cells)
26.
27. Tumor-Infiltrating Lymphocytes (TILs)
• Before the recent development of checkpoint
modulators (anti-PD-1), which shows a
comparable level of response, TILs had been the
only agent approved by the US FDA for patients
with metastatic melanoma.
• discovered to be mononuclear lymphocytes that
had a propensity to surround and invade tumors.
• These TILs were first discovered in resected
melanomas and were found to contain a mixture
of both CD4 and CD8 T cells.
28. TCR-Transduced T Cells
• TCR-transduced T cells are often generated via
genetic induction of tumor-specific TCR. This is
often done by cloning the particular antigen-
specific TCR into a retroviral backbone.
• TCR-transduced T cells present many advantages
and solutions to other immunotherapies. Most
importantly, there is a robust ability for TCR-
transduced T cells to be generated against a
plethora of tumor antigens.
31. Tisagenlecleucel
• Approved in 2017 for the treatment of children
and young adults with leukemia
• Approved in 2018 for adults with certain types of
non-Hodgkin lymphoma- specifically DLBCL, high-
grade B-cell lymphoma, and DLBCL that arises
from follicular lymphoma
Axicabtagene ciloleucel
• Approved in 2017 for the treatment of diffuse
large B-cell lymphoma(DLBCL)
32. • CARs contain the antigen-binding domain of a
monoclonal antibody to confer recognition of the
targeted tumor antigen coupled to intracellular
domains capable of activating T cells.
• When expressed in T cells, these CARs recognize cell
surface antigens and activate T cells independent of
antigen presentation by a MHC molecule as required
for physiologic antigen presentation.
• CAR targeting CD19, a B-cell antigen, resulted in
striking efficacy in patients with B-cell leukemias.
• Other CARs targeting CD22 and B-cell maturation
antigen (BCMA) have shown efficacy and are currently
under investigation.
33. Bispecific Antibodies to Engage T Cells
Blinatumomab
• Approved in 2018 for the treatment of adult and
pediatric patients with B-cell precursor acute
lymphoblastic leukemia(ALL)
• The benefits of bispecific antibodies (bsAbs) rely
on their ability to target 2 unique cell types and
direct immune effectors towards cancer cells.
• Blinatumomab is a CD3/CD19 bispecific antibody
that act by targeting the TCR on T cells (CD3) and
recruiting them to B cells (CD19).