IMMUNE RESPONSE TO TUMOR

Dr. Elyusrar A. Jalal Ph. D

CANCER : UNCONTROLLED GROWTH OF
TRANSFORMED CELLS

Single
transformed Tumor mass
malignant cell metastasis

Clone of
transformed
malignant cells
 TUMOR REJECTION ANTIGENS
RECOGNIZED BY THE IMMUNE SYSTEM

1. Point mutation in self protein during the process of oncogenesis

2. Cancer-testis antigens. Protein encoded by genes that are normally
expressed only in male germ cells in the testis. Male germ cells do not
express MHC molecules.
3. Differentiation antigens, protein encoded by gens that expressed only in
particular type of tissue.
4. Antigens that overexpressed in tumor cells compared with normal cells
5. Molecules that display abnormal post-translational modifications
6. Abnormal post-transcriptional modifications. Proteins that are generated
when one or more introns are retained in the mRNA
7. Proteins encoded by viral oncogens
TUMOR REJECTION ANTIGENS
(TRA)

Peptides of tumor-cell proteins that

are presented to T-cell by MHC
molecules

These peptides become the target

of a tumor-specific T-cell response
 Tumor rejection
antigens may arise by
point mutations in self
proteins, which occur
during the process of
oncogenesis.
Can be recognized by
mature T cells
 Tumor cells
downregulate
MHC class I
expression
IMMUNE SYSTEM INTERACTION WITH TUMOR
ELIMINATION OF TUMOR
IMMUNOSURVEILANCE
 IMMUNOTHERAPY

Using the immune response to

attact tumor
CONTROL TUMOR GROWTH
USING MONOCLONAL
ANTIBODY AGAINST TUMOR
ANTIGENS

Requires that a tumor specific

antigen be expressed on the tumor
cell surface
NK cells, ADCC (antibody-
dependent cell-mediated
cytotoxicity)
Antibody / fragmen of antibody
conyugated to toxin
Antibody conjugated to radioactive
substance
 Linking the antibody to a toxin (immunotoxin). The antibody
must be internalized to allow the cleavage of the toxin in the
endocytic compartment, allowing the toxin to penetrate and kill
the cell
Conyugated to chemotherapeutic drugs (adriamycin) or
radioisotopes
These have the advantage of also killing the neighboring tumor
cells
ENHANCING THE IMMUNE RESPONSE TO TUMORS
Vaccination:
1. Vaccine against human papiloma virus was 100% effective in preventing cervical cancer
2. Vaccines based on tumor antigens. Ideal approach to T-cell mediated immunotherapy, but
difficult to develop. Relevant peptide of tumor rejection antigens may not be shared
between different patients tumor
3. Cell-based vaccines, prepared by mixing tumor cells or tumor extract with adjuvants
4. Whole protein or peptide vaccines of identified tumor rejection antigen, administered
alone or presented by patients own dendritic cells
5. Vaccination based on isolation of heat-shock proteins from tumor cells. Dendritic cells
express receptors that mediate the uptake of certain heat-shock proteins and can deliver
the peptide into the antigen-processing pathways for presentation by MHC class I
molecules. The effectiveness is limited