Tumor Immunology

1. TumorImmunology • evidence for immune reactivity against tumor • changes in cellular characteristics due to malignancy • tumor and host components which affect tumor progression • use of tumor antigens in diagnosis and immunotherapy

2. Evidence for immunosurveillance Infiltration of malignant tissue

3. cause of immuno-deficiency malignancy • primary (inherited) immunodeficiency lymphomas lymphoma, cervical cancer, liver cancer, skin cancer, Kaposi’s sarcoma. • secondary (acquired) immunodeficiency • malaria Burkitt’s lymphoma • autoimmunity lymphoma Association between immunodeficiency and cancer

4. Tumors stimulate an immune response • Animals can be immunized against tumors • Immunity is transferable from immune to naïve animals • Tumor specific antibodies and cell have been detected in humans with some malignancies

5. Neo-antigens of immunologic significance on tumor cells • Oncofetal/differentiation antigens • Alpha-feto-protein (AFP) • Cracino embryonic antigen (CEA) • CALLA (common acute lymphoblastic leukemia antigen) • Tumor-associated transplantation antigens • Tumor specific transplantation antigen • Virus associated shared antigens

6. Alpha fetoprotein: clinical use AFP increases in testicular and liver cancers • Aids in diagnosis and staging • Patient management • Detection of tumors

7. Alpha fetoprotein: clinical use

8. Alpha fetoprotein: concentrations • Normal concentration: <20 ng/ml • Abnormal concentrations • 100-350 possible hepatoma • 350-500 probable hepatoma • 500-100 likely hepatoma • >1000 HEPATOMA

9. Carcinoembryonic antigen:clinical use • Adjunct in diagnosis • Staging and prognosis • Monitoring response to therapy • Detection of tumor recurrence

10. Carcinoembryonic antigen:clinical use

11. Carcinoembryonic antigen:clinical use CEA as a diagnostic adjunct • Symptomatic patient • Elevated value 5-10 times the upper limit Normal value <10ng/ml

12. Tumor associated transplantation antigens: shared Ag on virally induced tumors

13. Tumor associated transplantation antigens: unique Ag on chemically induced tumors

14. Immunity against tumor All components, specific and nonspecific, humoral and cellular affect tumor progression and growth

15. Escape from immunosurveillance Lack of Neo-antigens

16. Escape from immunosurveillance Lack of co-stimulatory molecules

17. Escape from immunosurveillance Lack of class I MHC

18. Escape from immunosurveillance Tumors secrete Immunosuppressive molecules

19. Escape from immunosurveillance Tumors shed their neo-antigens

20. Use of tumor associated antigens • Raise monoclonal antibodies • Use antibodies for diagnosis • Use antibodies for therapy • Stimulate the in vivo specific response • Specific active treatment • Specific passive treatment • Adjuvant therapy to augment specific immunity

21. Use of tumor associated antigensmonoclonal antibodies

22. Monoclonal antibodies:use as a diagnostic tool

23. killed tumor cells, purified or recombinant Ag specific non- specific BCG, Propionibacterium acne, levamisole, etc. non-specific LAK cells, cytokines antibodies alone or conjugated with other agent, activated T cells specific Immunotherapy of tumors active immunotherapy passive immunotherapy

24. Non-specific immunotherapy bacterial products BCG, P. acnes, muramyl dipeptide activate macrophages and NK cells (via cytokines) synthetic molecules pyran, poly I:C interferon production cytokines IFN-, IFN-, IFN-, IL-2, TNF- activate macrophages and NK cells

25. remission of hairy cell leukemia, weak effect on carcinomas increased expression of class-I MHC, possible anti tumor effect IFN-, - increased expression of class-I MHC, Tc and NK cell activation IFN- remission of ovarian carcinoma T cell proliferation and activation, NK cell activation remission in renal cell carcinoma and melanoma IL-2 macrophage and lymphocyte activation reduction in malignant ascites TNF- Cytokine immunotherapy

26. Genetic approaches to cancer treatment • Transfection with genes • Cytokines • Class I MHC • Co-stimulatory molecules