Date post: | 11-May-2015 |
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Tumor Immunology (II):
Cancer Immunotherapy
Masoud H. ManjiliDepartment of Microbiology &
ImmunologyGoodwin Research Building-286
(804) 828-8779
Learning Objective
Learn how to harness the immune system to kill tumors: 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 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
Tumor antigens
Tumor antigens
Tumor antigens
Immunotherapy
Adoptive T cell therapy (AIT)
Passive immunotherapy using antibodies
Active-specific immunotherapy by using vaccines
AIT + IL-2 against
melanoma
AIT + IL-2 against melanoma
Before After
Transfer tumor-specific T cell receptor genes using
retroviral vectors into patients’ T cell before AIT
AIT for B cell lymphoma
Passive immunotherapy
Passive immunotherapy
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
Anti-CD22 Ab fused to a fragment of Pseudomonas toxin in patients with B-cell leukemia (hairy-cell leukemia)
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
Signal I
Signal II
T cells
Tumor
Vaccination: cross presentation of
tumor antigens by APCsT cell activation T cell killer function
Vaccination
Cell-based vaccines using irradiated tumors with adjuvants such as BCG
Peptide- and protein-based vaccines
DNA vaccines
Vaccination: increase immunogenicity of tumor
cells
Vaccination
HPV vaccine for the prevention of cervical cancer
Oncophage (gp96): a tumor-derived heat shock protein vaccine against kidney cancer and melanoma
Vaccination: Oncophage
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
Janeway’s Immunobiology, 7th edition: Chapter 15; Pgs. 672-678