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Cancer Immunotherapy and Its Immunologic Complications PowerPoint Presentation

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Description : Check out this medical PowerPoint presentation titled "Cancer immunotherapy and its immunologic complications" by Abul K. Abbas.

This medical PowerPoint presentation is about cancer immunotherapy, a type of cancer treatment that works by stimulating the immune system to target and attack cancer cells. Immunotherapy drugs are designed to block certain proteins or pathways that inhibit the immune systems ability to recognize and destroy cancer cells.

While cancer immunotherapy has shown great promise in treating various types of cancer, it can also cause a number of immunologic complications. These complications can occur as a result of the immune system becoming overactive or mistakenly targeting healthy tissues.

One of the most common immunologic complications of cancer immunotherapy is autoimmune disorders. These occur when the immune system attacks healthy tissues, leading to conditions such as colitis, thyroiditis, and diabetes. Symptoms may include fever, rash, joint pain, and organ dysfunction.

Another potential complication is cytokine release syndrome (CRS). This occurs when immunotherapy drugs cause an overproduction of cytokines, which are proteins that regulate the immune system. The excess cytokines can cause a range of symptoms, including fever, fatigue, muscle pain, and difficulty breathing.

Immunotherapy can also cause immune-related adverse events (irAEs), which are side effects that affect organs such as the liver, lungs, and kidneys. These can be serious and require prompt medical attention.

Finally, immunotherapy can weaken the immune system, making patients more susceptible to infections. This is especially true for patients who are receiving combination therapy with multiple immunotherapy drugs.

To minimize the risk of immunologic complications, it is important for patients receiving cancer immunotherapy to be closely monitored by their healthcare team. Any new symptoms should be promptly reported to the healthcare provider. Additionally, patients should receive regular blood tests to monitor their immune system function and organ function.

Tags : Cancer immunotherapy, cancer treatment, Immunotherapy drugs, pharmaceuticals, pharmaceuticals PowerPoint presentations

Published on : Jun 23, 2023 | Views : 1374 | Downloads : 4

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1 Cancer immunotherapy and its immunologic complications Abul K. Abbas UCSF Abul.abbas@ucsf.edu
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General principles The immune system recognizes and reacts against cancers The immune response against tumors is often dominated by regulation or tolerance Evasion of host immunity is one of the hallmarks of cancer Some immune responses promote cancer growth Defining the immune response against cancers will help in developing new immunotherapies 2
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T cell responses to tumors 3
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Fridman et al. Nat Rev Cancer 12:298, 2012 Immune phenotypes that predict outcomes in different cancers 4 Becht et al. Adv Immunol 130:95, 2016
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Tumor antigens: Must be tumor-specific (not in normal cells) Must be capable of stimulating CD8 T cell responses in patients Most tumor antigens that elicit immune responses are neoantigens Produced by mutated genes that are usually not involved in oncogenesis and reflect genomic instability (passenger mutations) Cytosolic proteins so presented by class I MHC Mutations have to be in MHC-biding epitopes Not present normally, so no tolerance Types of tumor antigens 5
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Tumor immune evasion mechanisms Loss of MHC and proteins involved in antigen processing T cell exhaustion Repeated stimulation of T cells Tumors express PDL-1 Secretion of immunosuppressive molecules TGF-b, others 6
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Cancer vaccines Most attempts so far have tried to generate antibodies against surface antigens expressed on many tumors Generally unsuccessful because of lack of specificity, expression of antigen on normal cells, and inability of antibodies to provide protection Future attempts will rely on generating CTLs specific for tumor-specific neoantigens Identifying neoantigens in each tumor (personalized medicine) Difficult to generate good CTLs with vaccines Preventing escape mutants Have to overcome immune evasion mechanisms of tumor 8
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Passive immunotherapy 9
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10 Adoptive cell therapy Purify T cells (NK cells?) from blood or tumor infiltrate, expand in vitro, transfer into patients Major problem is low frequency of T cells specific for tumor antigens Attempts to overcome the problem by introducing tumor-specific antigen receptor into patient T cells Problems with introducing TCR? Tumors often lose MHC expression 10
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Development of chimeric antigen receptors VH VL 11
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Chimeric antigen receptor-T cell (CAR-T) therapy Remarkable success in B cell acute leukemia (targeting CD19); up to 90% complete remission Risk of cytokine storm Outgrowth of antigen-loss variants of tumors? 12
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Limitations and challenges of CAR-T cell therapy Cytokine release syndrome – many T cells respond to target antigen Not yet effective against solid tumors Resistance due to loss of target antigen Exhaustion of transferred T cells Technically challenging and expensive 13
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Cytokine release syndrome Caused by large number of T cells responding to target antigen Similar to septic shock Good clinical response with anti-IL6R (toclizumab) Some complications (e.g. encephalopathy) may not be as responsive as systemic complications 14
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Immune checkpoints Inhibitory receptors on T cells block activation CTLA-4: competes with CD28, reduces costimulation PD-1: activates phosphatase, blocks kinase-dependent signals from CD28 and TCR Many others described 15
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Tumors induce T cell exhaustion 16
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Blocking CTLA-4 promotes tumor rejection: CTLA-4 limits immune responses to tumors Administration of antibody that blocks CTLA-4 in tumor-bearing mouse leads to tumor regression 17
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Checkpoint blockade: Removing the brakes on the immune response Even more impressive results with anti-PD-1 in cancer patients 18
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Risks of blocking CTLA-4 or PD-1 Blocking a mechanism of self-tolerance leads to: 19
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Adverse effects of checkpoint blockade 20 Inevitable consequence of blocking essential mechanisms of self-tolerance: Autoimmune reactions From: June, Warshauser and Bluestone Nat Med 2017
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Autoimmune complications of checkpoint blockade Most often grade 1 or 2 Manageable with conservative therapy and withdrawal of immunotherapy More severe with combinations of checkpoint blockers Unusual features Anti-PD1/PDL1: brittle diabetes Anti-CTLA4: anterior pituitary inflammation Combination: myocarditis All: colitis, arthritis 21
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Response to checkpoint blockade 22 Haslam and Prasad, 2019
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Combination strategies for cancer immunotherapy Combinations of checkpoint blockers or one checkpoint blocker with another cancer treatment 23 Will inevitably cause more severe immune related adverse events From Galon and Bruni. Nat Rev Drug Discov 18:197, 2019