It's a complete description about tumor antigen from kuby's immunology.

1. TUMOR CELL
TUMOR ANTIGENS SWATHI PRABHAKAR
[810014214042]
III Year, B.Tech Biotech
Anna university [BIT Campus]
Trichy 620 024
swathipriyabiotechautbit@gmail.com

3.  Tumor antigen is an antigenic
substance produced in tumor cells.
i.e., it triggers an immune response
in the host.
 These antigens are not membrane
proteins but are derivatives of cytosolic
proteins.
i.e.,peptides of cytosolic proteins

4. Two types of tumor antigens have been
identified on tumor cells:
1. Tumor-Specific Transplantation Antigens
(TSTAs)
E.g. : Abnormal products of ras and p53 genes
2. Tumor-Associated Transplantation Antigens
(TATAs)
E.g. : Epidermal growth factor (EGF) like p97

5. Two genes-
red and blueTwo
proteins-
red and blue

6. Mutated
Pink gene
New altered protein

7. Irregular gene
expression
- Black colour
Unwanted
protein
production

8. Over expressed
Normal gene
Abnormal protein
concentration

9. 1. Unique to tumor cells
2. Do not occur on normal cells in the body.
3. TSTA produced due to physical, chemical or
viral mutagens
4. Mutation results in altered cellular proteins.
This cellular proteins on cytosolic processing
results in novel peptides i.e. tumor antigen

10. 4. This tumor antigen induces cell-mediated
immune response by tumor-specific
cytosolic T-cell (CTLs)
5. The immune system detects and eliminates
these tumor cells by the antigens on the cell
surface.

11. • Tumor-associated antigens are not unique to
tumor cells.
• These are proteins that are expressed on
normal cells during fetal development when the
immune system is immature and unable to
respond but that normally are not expressed in
the adult.

12. • Reactivation of the embryonic genes that
encode oncofetal proteins in tumor cells
results in their expression on the fully
differentiated tumor cells.
• Tumor-associated antigens may also be
proteins that are normally expressed at
extremely low levels on normal cells but are
expressed at much higher levels on tumor
cells.

13. • For example, Transferrin growth factor,
designated p97, which aids in the transport of
iron into cells. Whereas normal cells express
less than 8,000 molecules of p97 per cell,
melanoma cells express 50,000–500,000
molecules of p97 per cell

15. 1. Antigens encoded by genes exclusively
expressed by tumors.
2. Antigens encoded by variant forms of normal
genes that have been altered by mutation.
3. Antigens normally expressed only at certain
stages of differentiation or only by certain
differentiation lineages.
4. Antigens that are over expressed in particular
tumors

17. Following are causes of TSTA Production:
1. Chemical agents E.g. : Methylcholanthrene
2. Physical agents E.g. : Ultraviolet light
3. VIRUS E.g. : Polyoma virus (PV)

18. 1. Chemical agents/ Physical agents
-Antigens’ nature varies with respect to
1.1. The type of tissue administered
1.2. The dosage
2. VIRUS
- Antigens are specific only to strain
irrespective of tissue and concentration.

25. 1 2

26. 1
2

27. • In one method, peptides bound to class I MHC molecules on
the membranes of the tumor cells are eluted with acid and
purified by high-pressure liquid chromatography (HPLC). In
some cases, sufficient peptide is eluted to allow its sequence
to be deduced by Edman degradation.

28. In a second approach, cDNA libraries are prepared from tumor cells. These
cDNA libraries are transfected transiently into COS cells, which are monkey
kidney cells transfected with the gene that codes for the SV40 large-T
antigen. When these cells are later transfected with plasmids containing
both the tumor-cell cDNA and an SV40 origin of replication, the large-T
antigen stimulates plasmid replication, so that up to 104–105 plasmid
copies are produced per cell. This results in high-level expression of the
tumor-cell DNA.

29. 1. ONCOFETAL TUMOR ANTIGENS
E.g. :1. Alpha-fetoprotein (AFP) -Liver cancer
2.Carcinoembryonic antigen (CEA)- advanced
Colorectal cancer
2. ONCOGENE PROTEINS AS TUMOR ANTIGENS
E.g. : Human breast-cancer cells -Neu protein

30. Tumor antigens
Cell-mediated immune
responses
Humoral immune
responses
IMMUNE
SYSTEM
IMMUNE
SYSTEM
(Major)
(Minor)
TSTAs CTLs produced
against tumor antigens
But MHC count on tumor
cells reduces thus limiting
CTLs
Tumor antigens are
displayed by class I MHC

32. The recognition of tumor cells by NK
cells is MHC
restricted
Fc receptors on NK cells can bind
to antibody-coated tumor cells, leading
to ADCC.

34. The recognition of tumor cells by macrophages
are not MHC restricted
Macrophages
cluster around
Tumor cells
Mediates ADCC
utilising lytic
enzymes,
ROS,RNS.
Macrophages produces cytokine –
“TNF alpha” induceing hemorrhage
and necrosis of the tumor.

35. Immune surveillance theory conceptualized by Paul
Ehrlich-states “cancer cells frequently arise in the body but are
recognized as foreign and eliminated by the immune system”
Later Lewis Thomas suggested that the cell-mediated branch of
the immune system had evolved to patrol the body and eliminate
cancer cells.
Impairment in the immune response results in cancer.

36. 1.Nude mice (Lacking thymus and functional T cells) shows no
susceptible to cancer.
2. Individuals on immunosuppressive drugs do show an increased
incidence of cancers of the immune system, other common
cancers (e.g., lung, breast, and colon cancer) are not increased in
these individuals, contrary to what the theory predicts

37. 3. Effect of tumor-cell dosage on the ability of the immune
system to respond also are incompatible with the immune
surveillance theory. For example, animals injected with very low
or very high doses of tumor cells develop tumors, whereas those
injected with intermediate doses do not. The mechanism by
which a low dose of tumor cells “sneaks through” is difficult to
reconcile with the immune surveillance theory

38. 1.Finally, this theory assumes 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
2. Cancer cells and normal cells exhibit qualitative antigen
differences
3. An immune response can be generated to tumor cells, and
therapeutic approaches aimed at increasing that response may
serve as a defense against malignant cells tumor evasion of the
Immune

39. -ROBERT GREEN INGERSOLL