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