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Tumor Immunology (II): Cancer Immunotherapy

Tumor Immunology (II): Cancer Immunotherapy. Masoud H. Manjili Department of Microbiology & Immunology Goodwin Research Building-286 (804) 828-8779. Learning Objective. Learn how to harness the immune system to kill tumors: immunotherapy. Cancer Immunotherapy.

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Tumor Immunology (II): Cancer Immunotherapy

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  1. Tumor Immunology (II):Cancer Immunotherapy Masoud H. Manjili Department of Microbiology & Immunology Goodwin Research Building-286 (804) 828-8779

  2. Learning Objective • Learn how to harness the immune system to kill tumors: immunotherapy

  3. Cancer Immunotherapy How to kill tumors without killing normal cells? To induce an immune response against the tumor that would discriminate between the tumor and normal cells: Adaptive immunity

  4. Tumor antigens • Tumor Specific Antigens (TSA) • Are only found on tumors • As a result of point mutations or gene rearrangement • derive from viral antigens • Tumor Associated Antigens (TAA) • Found on both normal and tumor cells, but are overexpressed on cancer cells • Developmental antigens which become derepressed. (CEA) • Differentiation antigens are tissue specific • Altered modification of a protein could be an antigen

  5. Tumor antigens

  6. Tumor antigens

  7. Immunotherapy • Adoptive T cell therapy (AIT) • Passive immunotherapy using antibodies • Active-specific immunotherapy by using vaccines

  8. AIT + IL-2 against melanoma

  9. AIT + IL-2 against melanoma Before After

  10. Transfer tumor-specific T cell receptor genes using retroviral vectors into patients’ T cell before AIT

  11. AIT for B cell lymphoma

  12. Passive immunotherapy

  13. Passive immunotherapy

  14. Passive immunotherapy: mAbs • Herceptin: anti-HER-2/neu in breast cancer patients • Rituximab: anti-CD20 in patients with non-Hodgkin’s lymphoma • Bevacizumab: anti-VEGF in patients with advanced colorectal cancer Limitations: clearance by soluble Ags, antigenic variation of the tumor, inefficient killing or penetration into the tumor mass

  15. Passive immunotherapy: immunotoxins • Anti-CD22 Ab fused to a fragment of Pseudomonas toxin in patients with B-cell leukemia (hairy-cell leukemia)

  16. Passive immunotherapy: drug-linked antibodies • Anti-CD20 antibodies linked to a radioisotope yttrium-90 in patients with refractory B-cell lymphoma • Antibody-directed enzyme/pro-drug therapy (ADEPT): Antibodies linked to an enzyme that metabolizes a nontoxic pro-drug to the active cytotoxic drug

  17. Signal I T cells Tumor Signal II Vaccination: cross presentation of tumor antigens by APCs T cell activation T cell killer function

  18. Vaccination • Cell-based vaccines using irradiated tumors with adjuvants such as BCG • Peptide- and protein-based vaccines • DNA vaccines

  19. Vaccination: increase immunogenicity of tumor cells

  20. Vaccination • HPV vaccine for the prevention of cervical cancer • Oncophage (gp96): a tumor-derived heat shock protein vaccine against kidney cancer and melanoma

  21. Vaccination: Oncophage

  22. Summary • Manipulation of tumors for the expression of new antigens is a promising approach for the induction of anti-tumor immune responses • Vaccines may be effective against residual tumors but AIT and passive immunotherapy have potentials for the treatment of primary tumors

  23. Suggested Reading Janeway’s Immunobiology, 7th edition: Chapter 15; Pgs. 672-678

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