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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

Tumor Immunology (II):Cancer Immunotherapy

Masoud H. Manjili

Department of Microbiology & Immunology

Goodwin Research Building-286

(804) 828-8779

learning objective
Learning Objective
  • Learn how to harness the immune system to kill tumors: immunotherapy
cancer immunotherapy
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

tumor antigens
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
immunotherapy
Immunotherapy
  • Adoptive T cell therapy (AIT)
  • Passive immunotherapy using antibodies
  • Active-specific immunotherapy by using vaccines
slide10
Transfer tumor-specific T cell receptor genes using retroviral vectors into patients’ T cell before AIT
passive immunotherapy mabs
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

passive immunotherapy immunotoxins
Passive immunotherapy: immunotoxins
  • Anti-CD22 Ab fused to a fragment of Pseudomonas toxin in patients with B-cell leukemia (hairy-cell leukemia)
passive immunotherapy drug linked antibodies
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
slide17

Signal I

T cells

Tumor

Signal II

Vaccination: cross presentation of

tumor antigens by APCs

T cell activation

T cell killer function

vaccination
Vaccination
  • Cell-based vaccines using irradiated tumors with adjuvants such as BCG
  • Peptide- and protein-based vaccines
  • DNA vaccines
vaccination1
Vaccination
  • HPV vaccine for the prevention of cervical cancer
  • Oncophage (gp96): a tumor-derived heat shock protein vaccine against kidney cancer and melanoma
summary
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
suggested reading
Suggested Reading

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