cancer immunology & cancer immunotherapy

2. .
..
By
Ashwani Kesarwani
M.Sc IInd sem
Presentation on
cancer immunology &
cancer
immunotherapy

3. Introduction
CANCER IMMUNOLOGY-
It is the study of interaction between immune
system & cancer cell (also called Tumors or
malignancies).
• TUMOR- Cells that continue to replicate, fail
to differentiate into specialized cells, and
become immortal.
MalignantBenign

4. ,

5. Types of Cancer
Carcinoma: arising from epithelial tissue, such as
glands, breast, skin, and linings of the urogenital,
digestive, and respiratory systems.
Sarcoma: solid tumors of muscles, bone, and
cartilage that arise from the mesoderm connective
tissue.
Leukemia: disease of bone marrow causing
excessive production of leukocytes.
Lymphoma: diseases of the lymph nodes and
spleen that cause excessive production of
lymphocytes.

6. ONCOGENES
A gene that has the potential to cause cancer.
Oncogenes may also be found in normal cells.
The cellular ones (c-onc) in contrast to the viral
ones (v-onc) are called “PROTO-
ONCOGENES”
A proto-oncogene is a normal gene that can
become an oncogene due to mutation or
increased expression.
60-100 different proto-oncogenes have been
identified.

7. .
Functional classification of cancer
associated genes
GENES THAT REGULATE
PROGRAMMED CELL
DEATH.
Eg- bcl-2 etc.
TUMOR-SUPRESSOR
GENES, INHIBITORS OF
CELLULAR
PROLIFERATION.
Eg- p53 etc.
GENES THAT INDUCE
CELLULAR
PROLIFERATION.
Eg- sis, fms, erbB,
neu etc.

8. Conversion of Proto-oncogenes to oncogenes

9. Tumor Antigens
Cell-surface protein present on the surface
of tumor cells that can-mediate immune
response.
Some are found only on tumor cells;
others are also found on normal cells.
TUMOR ANTIGENS
Tumor-associated
transplantation antigens
(TATAs)
Tumor-specific
transplantation antigens
(TSTAs)

10. Tumor-Specific Antigens
Unique to tumor cells and do not occur on
normal cells in the body.
These are identified on tumors, induced with
chemical or physical carcinogens and on some
virally induced tumors.
CHEMICALLY OR PHYSICALLY INDUCED
TUMOR ANTIGENS-
Methylcholanthrene and
ultraviolet light

11. Chemical-induced tumors
(Methylcholanthrene)

12. Virally induced tumor antigens
Virally induced tumors express tumor antigens
shared by all tumors induced by the same virus.
When syngeneic mice are injected with killed
cells from a particular SV40 or polyoma-
induced tumor, the recipients are protected
against subsequent challenge with live cells
from any SV40 or polyoma-induced tumors.
Likewise, when lymphocytes are transferred
from mice with a virus-induced tumor into
normal syngeneic recipients, the recipients
reject subsequent transplants of all syngeneic
tumors induced by the same virus.

13. Virally induced Tumor antigens
.

14. Animal models to show the potential value of
virally induced tumor antigens
In one experiment, mice immunized with a
preparation of genetically engineered polyoma
virus tumor antigen were shown to be immune to
subsequent injections of live polyoma-induced
tumor cells.
In another experiment, mice were immunized
with a vaccinia-virus vaccine engineered with
the gene encoding the polyoma-tumor antigen.
These mice also developed immunity, rejecting
later injections of live polyoma-induced tumor
cells.

15. TUMOR-ASSOCIATED ANTIGENS
These tumor associated transplantation
antigens may be proteins usually
expressed only on fetal cells but not on
normal adult cells.
They may be proteins expressed at low
levels by normal cells but at much higher
levels by tumor cells.
Example- transferrin growth factor,
designated p97 (aid in transport of iron
into cells).

16. Oncofetal tumor antigen
Found not only on cancerous cells but
also on normal fetal cells.
Appear only in embryonic development,
before the immune system acquires
immunocompetence.
If appear late in cancer cells, they are
recognized as non-self and induce an
immunologic response.
Example- Alpha-fetoprotein (AFP) &
carcinoembrionic antigen(CEA).

17. Examples of tumor antigens

18. IMMUNE RESPONSE TO TUMORS
Tumor antigens can be shown to induce
both humoral and cell-mediated immune
responses that result In the destruction of the
tumor cell.
[1] Role of Cytotoxic T Lymphocytes (CTL)
Tumour antigens associate with MHC class I molecule on
surface of tumours.
CTL recognise tumour cells with MHC class I.
Bind to them and release TNF- - toxicity to tumour cell -
tumour cell killing.

19. .
[2] Natural Killer Cells (NK Cells)
Capable of lysing a wide variety of tumour cells.
NK cells recognise this and attack the tumour
cell “Antibody-Dependent Cell-Mediated
Cytotoxicity” (ADCC)
NK cells release TNF- & NK cytotoxic factor.
[3] Macrophages
Activated macrophages secrete lytic enzymes.
Also secrete TNF-.
Secrete nitric oxide (potential antitumour
effects).

20. IMMUNE SURVEILLANCE THEORY
First conceptualized in the early 1900s by Paul
Ehrlich.
Cancer cells frequently arise in the body but are
recognized as foreign and eliminated by the
immune system.
The basic concept of the immune surveillance
theory— Malignant tumors arise only if the
immune system is somehow impaired or if the
tumor cells lose their immunogenicity, enabling
them to escape immune surveillance.

21. Cancer immunotherapy
Use of immune system to reject
cancer.
Several types of Cancer
immunotherapy in current use
are-

22. .
.
tumor CTL
CD28
tumor
B7
No killing
No T cell
activation
Killing
T cell
activation
Manipulation of co-stimulatory signals
CTL
TCR
MHC class I Ag

23. Systemic Cytokine Therapy for Tumors

24. .
Use of LAK cells + IL-2 to treat cancer
Isolate lymphocytes
from blood
lymphocytes
+IL-2 for
3 days
IL-2
LAK
cells
melanoma
LAK- lymphokine activated killer cells

25. Treatment of Melanoma with
LAK cells +IL-2
.
.
Before After

26. .
.
Use of tumor-infiltrating lymphocytes + IL-2
to treat cancer
surgical removal
of cancer nodule
tumor
T cell
+IL-2
IL-2
Treatment of melanoma and renal cell carcinoma
lymphodepletion

27. .
.
Fig-Treatment of Melanomas with TIL + IL-2
Before After

28. Fig-Treatment of B-cell lymphoma with monoclonal antibody
specific for idiotypic determinants on the cancer cells

29. Monoclonal antibodies
.

30. Cancer vaccines

31. SUMMARY
Tumor antigens are recognized by immune
system
Immune response mainly mediated by CTL,
NK cells and macrophages
Immunotherapy aims at activating the
patient’s own immune system to fight the
tumor.

32. References
Kuby immunology (4th edition), Richard
A. Goldsby, Thomas J. Kindt, Barbara A.
Osborne.
Cellular & molecular immunology (5th
edition), Abdul K. Abbas, Andrew H.
Lichtman.
Immunology (6th edition), Ivan Roitt,
Jonathan Brostoff, David Male.