Tumor antigen

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

1. TUMOR CELL TUMOR ANTIGENS TUMOR ANTIGEN SWATHI PRABHAKAR [810014214042 ] III Year, B.Tech Biotech Anna university [BIT Campus] Trichy 620 024 [email protected]

2. OVERVIEW 1.TUMOUR ANTIGEN 2.Classification 3.PROPERTIES 3.1.Tumor-specific transplantation antigens (TSTAs) 3.2. Tumor-associated transplantation antigens (TATAs) 4.Classification based on T -cell recognition 5.Tsta producING AGENTS 6.SPECIFICITY OF AGENTS IN TSTA 7.IDENTIFICATION OF TSTA INDUCING GENE 8.Characterization of TSTA 9.Tumor-associated transplantation antigens (TATAs)-types 10.Immune Response against Tumor 11.NK Cells in Tumor Recognition 12.Macrophages in Tumor Recognition 14.IMMUNE SURVEILLANCE THEORY OBSERVATIONS

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 1.TUMOUR ANTIGEN

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

5. 2.Classification Two genes- red and blue Two proteins- red and blue

6. 2.Classification Mutated Pink gene New altered protein

7. 2.Classification Irregular gene expression - Black colour Unwanted protein production

8. 2.Classification Over expressed Normal gene Abnormal protein concentration

9. 3.PROPERTIES Unique to tumor cells Do not occur on normal cells in the body. TSTA produced due to physical, chemical or viral mutagens Mutation results in altered cellular proteins. This cellular proteins on cytosolic processing results in novel peptides i.e. tumor antigen 3.1.Tumor-specific transplantation antigens (TSTAs)

10. 3.PROPERTIES 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. 3.1.Tumor-specific transplantation antigens (TSTAs)

11. 3.PROPERTIES 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. 3.2. Tumor-associated transplantation antigens (TATAs)

12. 3.PROPERTIES 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. 3.2. Tumor-associated transplantation antigens (TATAs)

13. 3.PROPERTIES 3.2. Tumor-associated transplantation antigens (TATAs) 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. 3.PROPERTIES 3.2. Tumor-associated transplantation antigens (TATAs)

15. 4.Classification based on T -cell recognition 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. 4.Classification based on T -cell recognition 3.2. Tumor-associated transplantation antigens (TATAs)

17. 5.Tsta producING AGENTS Following are causes of TSTA Production: Chemical agents E.g. : Methylcholanthrene Physical agents E.g. : Ultraviolet light VIRUS E.g. : Polyoma virus (PV)

18. 6.SPECIFICITY OF AGENTS IN TSTA 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. 6.SPECIFICITY OF AGENTS IN TSTA

20. 6.SPECIFICITY OF AGENTS IN TSTA

21. 7.IDENTIFICATION OF TSTA INDUCING GENE

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24. 8.Characterization of TSTA 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 .

25. 8.Characterization of TSTA 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 .

26. 9.Tumor-associated transplantation antigens (TATAs)-types 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

27. 10.Immune Response against Tumor 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

28. 10.Immune Response against Tumor

29. 11.NK Cells in Tumor Recognition 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. 1

30. 11.NK Cells in Tumor Recognition

31. 12.Macrophages in Tumor Recognition 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. 2 3 1

32. 13.IMMUNE SURVEILLANCE THEORY 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.

33. 13. IMMUNE SURVEILLANCE THEORY-Contrary statements 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

34. 13 . IMMUNE SURVEILLANCE THEORY-Contrary statements 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

35. 13.IMMUNE SURVEILLANCE THEORY -OBSERVATIONS 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

36. Reason Observation And Experience -the holy trinity of science  Lovingly  SWATHI PRABHAKAR -ROBERT GREEN INGERSOLL