![Cancer Vaccines under clinical trials
• Bladder cancer
• Brain tumors
• Breast cancer
• Cervical cancer
• Colorectal cancer
• Kidney cancer
• Leukemia
• Lung cancer [Clinical trials with target antigens
include MAGE-3 (found in 42%) and NY-ESO-1 (found
in 30%). Others target antigens are such as p53,
survivin, and MUC1]
• Melanoma
• Myeloma
• Pancreatic cancer](https://image.slidesharecdn.com/presentation11-170524084825/85/Cancer-Immunotherapy-37-320.jpg)
Cancer Immunotherapy
- 2. Immune System Bacteria Virus Fungi Cancer Cells 1. Senses/ detects of pathogen 2. Mount an immune response
- 3. Immunity
- 4. Organ of the Immune System
- 5. Immune Cells and their Generation
- 10. Time Course of an Immune Response
- 11. Immunotherapy • Cancer Immunotherapy Therapy aimed to enhance the power of host immune system for the treatment of malignancy • Goals –↑ Antitumor Response –↓ Immunosuppresssion –↑ Immunogenicity of Tumors
- 12. Mechanism • Stimulating body`s own immune system to work strongly or smartly to attack on cancer cells • Giving immune system component, such as recombinant immunological proteins
- 13. Coley`s Toxin
- 15. Rituximab (Rituxan) and Trastuzumab (Herceptin) mABs were approved during the late 1990s to treat Lymphoma and Breast Cancer W.H.O. Approved First Immunotherapy
- 16. The History of Cancer Immunotherapy: from empirical approaches to rational, science-based therapies
- 17. Passive Immunotherapy • Administration of monoclonal antibodies which target either tumour-specific or over-expressed antigens Active Immunotherapy • Cytokines- IL-2 / Interferons / Tumour Necrosis Factor-alpha • Cancer vaccines • Cell-based therapies • Tumour-specific Cytotoxic T-cells • Tumour-derived Antigen Presenting Cells • Dendritic cells priming Types of Immunotherapy
- 18. Approaches of Immunotherapy • Monoclonal Antibodies • Non-specific Immunotherapies • Oncolytic Virus Therapy • T-cell Therapy • Cancer Vaccines
- 20. Types of Monoclonal Antibodies
- 21. ADEPT: antibody directed enzyme pro drug therapy; ADCC: antibody dependent cell-mediated cytotoxicity; CDC: complement dependent cytotoxicity; scFv : single-chain Fv fragment mAB Therapy
- 22. • Monoclonal antibodies are given intravenously • Monoclonal antibodies that bind only to cancer cell- specific antigens and induce an immunological response against the target cancer cell • Naked mAbs: antibodies that work by themselves. boost a person’s immune response against cancer cells • blocking specific proteins that help cancer cells grow eg. Trastuzumab-HER2 • Conjugated mAbs: mABs attached with a chemotherapeutic drug, radioactive particle or a toxin • Radiolabelled: Ibritumomab tiuxetan and tositumomab – CD20 antigen • Chemolabeled: brentuximab vedotin -CD30 antigen • Immunotoxins: denileukin diftitox mAB Therapy
- 24. Immune Checkpoint Inhibitors (mABs) PD-1 pathway T-cells & Pro B-cells CTLA-4 pathway T-cells & Tregs-cells •Activation of above the pathways, down-regulates the immune system and promoting self-tolerance by suppressing T-cell inflammatory activity • Immune Checkpoints • Immune Checkpoint Inhibitors, like Ipilimumab (Yervoy) Nivolumab (Opdivo) Pembrolizumab (Keytruda)
- 25. Possible Side Effects of mABs Treatment mAB is protein, may cause allergic reaction More common side effects while the drug is first being given: • Fever • Chills • Weakness • Headache • Nausea • Vomiting • Diarrhea • Low blood pressure • Rashes Compared with chemotherapy drugs, naked mAbs tend to have fewer serious side effects
- 26. Non-specific Immunotherapies/ Cytokine Therapy • Boost immune system to destroy cancer cells • Given as stand-alone or adjuvant with chemotherapy or radiation therapy Non-specific Immunotherapy Interferons (IFNs) Interleukins (ILs)
- 27. Interleukins • Recombinant IL-2 is approved to treat advanced kidney cancer and metastatic melanoma • Other interleukins, such as IL-7, IL-12, and IL-21, are now being studied • Side effects of IL-2 can include flu-like symptoms, weight gain, nausea, vomiting, diarrhea or low blood pressure • Rare and serious side effects include an abnormal heartbeat, chest pain and other heart problems
- 28. Interferons • 3 types: IFN-alfa, IFN-beta and IFN-gamma • Only IFN-alfa is used to treat cancer such as • Hairy cell leukemia • Chronic myelogenous leukemia (CML) • Follicular non-Hodgkin lymphoma • Cutaneous (skin) T-cell lymphoma • Kidney cancer • Melanoma • Side effects include: • Flu-like symptoms • Low white blood cell counts (which increase the risk of infection) • Skin rashes • Thinning hair
- 29. Signaling pathways of IFNs that mediate anti- tumor responses
- 31. • In October 2015, the U.S. F.D.A. approved the first oncolytic virus therapy to treat melanoma • The virus used in the treatment is called talimogene laherparepvec (Imlygic), or T-VEC • The virus is genetically modified version of the herpes simplex virus • T-VEC can inject directly into areas of melanoma Side effects can include: • Fatigue • Fever • Chills • Nausea • Flu-like symptoms • Pain at the injection site
- 32. T-Cell Therapy
- 34. • Researchers are still studying this and other ways of modifying T cells to treat cancer • Currently, these treatments are only available in clinical trials
- 35. Cancer Vaccine • Vaccine is a pre-exposes of the immune system to an antigen, thus boost immune system to fight cancer • There are 2 types of cancer vaccines: • Prevention vaccine (HPV and Hepatitis B) • Treatment vaccine (Sipuleucel-T)
- 36. Sipuleucel-T (Provenge) In 2010, FDA approved Provenge for men with metastatic prostate cancer Prostatic Acid Phosphatase Granulocyte-Macrophage Colony Stimulating Factor
- 37. Cancer Vaccines under clinical trials • Bladder cancer • Brain tumors • Breast cancer • Cervical cancer • Colorectal cancer • Kidney cancer • Leukemia • Lung cancer [Clinical trials with target antigens include MAGE-3 (found in 42%) and NY-ESO-1 (found in 30%). Others target antigens are such as p53, survivin, and MUC1] • Melanoma • Myeloma • Pancreatic cancer
- 38. Rational of Immunotherapy Combination Use of anit-CTLA-4 monoclonal antibody (Ipilimumab) as immune checkpoint inhibitor in advance melanoma improved overall survival (OS) of patient Remarkable anti-tumor activity of PD-1/ PD-L1 inhibition in melanoma, renal cancer cell and NSCLC provide proof- of-concept for efficacy of immunotherapy But Clinical efficacy of PD-1 pathway inhibition as monotherapy is limited with response rates of 20% or less
- 39. Thus, “Combination Therapy” will likely be required to enhance and broaden the anti-tumor activity of immunotherapy
- 40. Approaches for Combinatorial Immunotherapy • Novel cancer vaccines, • Oncolytic virus • Stimulation of co-stimulatory molecules • Targeted therapy (such as BRAF/MEK and ALK inhibition • Radiation/chemotherapy • Adoptive T-cell therapy (T-cells, CARs) Strategies that primarily address additional immunosuppressive mechanisms in the tumor microenvironment such as • Indoleamine 2,3-dioxgenase (IDO)- inhibition • TGF-β blockade • Regulatory T-cell (Treg) depletion • Angiogenesis inhibition
- 41. Everyone`s Company Everyone`s Growth Narendra D. Modi Hon'ble Prime Minister of India
- 42. References • Parker BS, Rautela J1, Hertzog PJ. Antitumour actions of interferons: implications for cancer therapy. Nat Rev Cancer, 2016,16(3),131- 44. • Ott PA, Hodi FS, Kaufman HL, Wigginton JM, Wolchok JD. Combination immunotherapy: a road map. J Immunother Cancer, 2017, 5-16. • Farkona S, Diamandis EP, Blasutig IM. Cancer immunotherapy: the beginning of the end of cancer ? BMC Med., 2016 May, 14-73. •Melero I, Berman DM, Aznar MA, Korman AJ, Pérez Gracia JL, Haanen J. Evolving synergistic combination of targeted immunotherapies to combat cancer. Nat Rev Cancer, 2015 Aug,15(8),457-72. • Cancer Immunotherapy - American Cancer Society (https://www.cancer.org ) • Understanding Immunotherapy (Cancer.Net)