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TUMOR CELL
TUMOR ANTIGENS SWATHI PRABHAKAR
[810014214042]
III Year, B.Tech Biotech
Anna university [BIT Campus]
Trichy 620 024
swathipriyabiotechautbit@gmail.com
 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
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
Two genes-
red and blueTwo
proteins-
red and blue
Mutated
Pink gene
New altered protein
Irregular gene
expression
- Black colour
Unwanted
protein
production
Over expressed
Normal gene
Abnormal protein
concentration
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
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.
• 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.
• 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.
• 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
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
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)
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.
1 2
1
2
• 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.
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.
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
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
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.
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.
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.
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
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
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
-ROBERT GREEN INGERSOLL

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Tumor antigen

  • 1. TUMOR CELL TUMOR ANTIGENS SWATHI PRABHAKAR [810014214042] III Year, B.Tech Biotech Anna university [BIT Campus] Trichy 620 024 swathipriyabiotechautbit@gmail.com
  • 2.
  • 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
  • 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
  • 14.
  • 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
  • 16.
  • 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.
  • 19.
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  • 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
  • 31.
  • 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.
  • 33.
  • 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