Downloaded 30 times
Uploaded bysivasankar. P
Cancer immunotherapy
This document discusses adaptive immunity in cancer therapies. It provides an overview of the history of cancer immunotherapy from ancient times to modern immunotherapy approaches. It describes the key players in the anti-tumor immune response including T cells, B cells, macrophages, and dendritic cells. Different immune-based therapy approaches are summarized, including monoclonal antibodies, cytokines, vaccines, manipulation of costimulatory signals, blocking inhibitory pathways, adoptive T cell therapy, and oncolytic virotherapy. The conclusion states that immunotherapy has shown effectiveness for some cancer types but has not been proven as an effective sole treatment for cancer.
More Related Content
Similar to Cancer immunotherapy
Cancer immunotherapy
- 1. Presented by : Sivasankar. P ADAPTIVE IMMUNITY IN CANCER THERAPIES
- 2. Introduction • Cancer immunotherapy–enhancing ani tumour immune response • mAb, T cells, cytokines, vaccines • Active or passive
- 3. Cancer immunotherapy • 1600BC –surgery • 1896-radiotherapy • • 1942-chemotherapy • 1976-immunotherapy • In 1891 -William B Colley-coleys toxins bacterial products for bone carcinoma • Why cancer immunotherapy important ? - Memory - Specific William B colley
- 4. Key players ofanti tumour immune response • Mostly cell mediated • Adaptive immunity • T cytotoxic cell • B cell • T helper cell • TREG cell • Innate immunity • Macrophage • Dentritic cell • NK cell • Complement system
- 5. How the immunesystem attacks the cancer cell T cell activation is the heart of immunotherapy
- 6. Different immune basedtherapies 1. Monoclonal antibodies 2. Cytokines 3. Vaccines 4. Manipulation of costimulatory signals 5. Blocking inhibitory pathways 1.CTLA-4 blockers 2.PDL1/PD1 blockers 6. Adoptive T cell therapy
- 7. 1.Monoclonal antibodies • Targetstumour antigens • Flagging targeted cancer cells for destruction • Blocking growth signals and receptors-trastuzumab • Marking for destruction • Naked mAb-anti CD 20 (Rituximab)- non hodgkins lymphoma • Stimulating apototic pathway • Anti-CD30 Brentuximab
- 8. Contd… • Guided missiletherapies –immunotoxins , • Ricin,diptheria toxin or cytokine conjugated • Chemotherapeutic drug conjugated • radioisotope conjugated ex: Ibritumomab & Tositumomab
- 9.
- 10. 2.Cytokines • IFN alpha(intronA) ,beta ,gamma (malignant melanoma) • TNF- alpha, beta • GM-CSF- sargramostim (Leukine) • IL-2,4,6,12 • IL-2 (proleukin) licensed for advanced kidney cancer & melanoma • TLR agonist imiquimod (Aldara, Zyclara), binds to specific toll-like receptors, basal cell carcinoma ,skin cancers.
- 11. Interferons • Most clinicaltrials involve IFN-α • Has been shown to induce tumor regression in hematologic malignancies i.e. leukemias, lymphomas, melanomas and breast cancer • All types of IFN increase MHC I expression • IFN-γ also has also been shown to increase MHC II expression on macrophages and increase activity of Tc cells, macrophages, and NK cells
- 12. INTRON ALPHA 2b(merck) •FDA approved for AIDS related kaposi carcoma • Hairy cell leukemia • Melanoma • Nom-hodgkins lymphoma
- 13. Proleukin(IL-2) • Skin, kidneycancer,kaposis sarcoma • contains IL-2 • Capillary leak syndrome • DNA recombinant technology • Stimulates production of TNF-a IL-1,IFN-Y • Induction of LAK cell • Exact mechanism unknown
- 14. GM-CSF- sargramostim • GM-CSFis a cytokine that stimulates the bone marrow, promoting immune and blood cell growth and dendritic cell development. • The drug sargramostim (Leukine) is currently being used and studied as a boost when given with other types of immunotherapy
- 15. TLR agonist • Theimmune system often detects germs through a series of receptors (called toll like receptors) found on the surface of most immune cells. • Several of these specialized receptors have been evaluated for use in cancer, • one such agent, imiquimod (Aldara, Zyclara), bindsto specific toll likereceptors,resulting in an immune response that kills cancer cells in patients with basal cell carcinoma and possibly other early-stage skin cancers.
- 16. Non specific stimulationof immune system • Modified bacteria • Intra vesicular BCG vaccine - bladder cancer • bacteria act as adjuvant and activates macrophage &T cells • Bacillus CalmetteGuerin (BCG), approved to treat bladder cancer, is tuberculosis bacteria modified to ensure they will not spread disease. • Treatment causes inflammation in the bladder that stimulates an immune response and guides immune cells to the bladder.
- 17. 6.Adoptive T celltherapy • Anti tumour actively cultured immune cells transferred into tumour bearing host • TIL (NK cells ) activated with IL-2 called LAK cells • Chimeric antigen receptor T cells • Used in metastatic melanoma • This type of immunotherapy treatment is still investigational and available only through clinical trials. • Studies haves shown promise in the treatment of leukemia lymphoma, metastaticmelanoma,neuroblastoma and synovial cell sarcoma. (June et al.,2015)
- 18. CAR-T cells Antigen specific domain CAR-Tcells (Chimeric antigen receptor-T cells0 T cells transduced with tumor-specific CAR CAR: Single fusion molecule with antigen specificity plus signaling domain cancer: Solid tumor & hematological malignancies Maus M V et al. Blood 2014;123:2625-2635 “Live drug” Tumor recognition independent of HLA (no HLA typing needed) Multiple anti- tumor immuno- modulators can be engineered Target variety of antigens (protein, carbohydrate, glycolipid) Advantages of CAR T cells
- 19. 3.Vaccines • Dentritic cellvaccine • Prevents metastasis after surgical removal-melanoma • Ex:sipuleucel-T(provenge)-prostate cancer • Fusion protein contain two parts 1.PAP 2.GM-CSF (Bergman et al.,2007)
- 20.
- 21. Contd… • Prophylactc HPVvaccine – cervical cancer • poultry – mareks disease • Cat –feline leukemia virus • DNA vaccine
- 22. Oncept • Xenogeneic DNAvaccine Oncept which was approved by the USDA for use in canine oral melanoma in 2007 • Another genetic vaccine that has been pursued in canine clinical trials encodes a catalytically inactive form of dog telomerase reverse transcriptase (dTERT) (Bergman et al.,2006) (Peruzzi et al.,2010)
- 23. 4.Manipulation of costimulatorysignals • Cancer cells lack costimulation • Tumour cells transfected with B7 gene or IL-2
- 24.
- 25. 5.Blocking inhibitory pathways •CTLA-4 blocker -(iplimumab) • Blocking of PDL1 /PD1 pathway (pembrolizumab)
- 26. Yervoy • An intravenous(IV) injection, was approved in 2011 • First-line treatment for unresectable metastatic melanoma. • It works by blocking the CTLA-4 checkpoint to allow a more lasting response against the cancer • Side effects for this drug often include diarrhea, fatigue, itching and skin rash.
- 27. Contd… (Hodi et al.,2010)
- 28. Blocking of PDL1/PD1 pathway Suppression of T-cell by by expressing PD-1L (Regan et al.,2016)
- 29.
- 30. Contd… • Pembrolizumab (Keytruda)and nivolumab (Opdivo) are IV injections, both approved in 2014 as second-line treatment for patients with metastatic melanoma who are no longer helped by ipilimumab • Clinical trials are also studying the effectiveness of combining CTLA-4 and PD-1 checkpoint inhibitor drugs to create a longer lasting immune response against melanoma
- 31. Oncolytic virotherapy • Oncolyticviruses (OV), which preferentially infect and lyse cancer cells • Adenoviruses(H101)-head &neck cancer ,reo virus, polio virus - glioblastoma • Oncolytic viruses were originally designed to induce “acute tumor debulking” following direct lysis of the tumor cells • China approved the use of a recombinant adenovirus (Oncorine) (Lichty et al.,2014)
- 32. CONCLUSION • Immunotherapy ofmalignancy employs various preparation for augmentation of tumour specific as well as non specific immune responses • Immunotoxins with monoclonal antibodies currently being tested • Though some articles saying immunotherapy is effective for some types of cancer ,to date immunotherapy has not been proved to be an effective treatment of cancer when used either alone or in conjunction with chemotherapy ,radiotherapy or surgery
- 33. References: 1.Berzofsky JA, MTerabe, S Oh, IM Belyakov, JD Ahlers, JEJanik, and JC Morris. Progress on new vaccine strategies for the immunotherapy and prevention of cancer. Journal ofClinical Investigation 113:1515-1525, 2004. 2.Curiel TJ. Regulatory T cells and treatment of cancer. Current Opinions in Immunology20:241-246, 2008. 3.Dranoff G. Cytokines in cancer pathogenesis and cancer therapy.Nature Reviews Cancer 4:11-22, 2004. 4.Farkas AM, and OJ Finn. Vaccines based on abnormal selfantigens as tumor associatedantigens: immune regulation. Seminars in Immunology 22:125-131, 2010. 5.Gattinoni L, DJ Powell Jr, SA Rosenberg, and NP Restifo. Adoptive immunotherapy for cancer: building on success. NatureReviews Immunology 6:383-393, 2006. 6.Gilboa E. DC-based cancer vaccines. Journal of Clinical Investigation 117:119 1203,2007. 7.Laheru DA, DM Pardoll, and EM Jaffee. Genes to vaccines forimmunotherapy: how the molecular biology revolution hasinflenced cancer immunology. Molecular Cancer Therapy 4:1645-1652, 2005.