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  • 1. Tumor Immunology
    • 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. Association between immunodeficiency and cancer
    • primary (inherited) immunodeficiency
    lymphomas Burkitt’s lymphoma
    • malaria
    • secondary (acquired) immunodeficiency
    lymphoma, cervical cancer, liver cancer, skin cancer, Kaposi’s sarcoma.
    • autoimmunity
    lymphoma malignancy cause of immuno-deficiency
  • 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.
    • CEA as a diagnostic adjunct
      • Symptomatic patient
      • Elevated value 5-10 times the upper limit
      • Normal value <10ng/ml
    Carcinoembryonic antigen: clinical use
  • 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 antigens monoclonal antibodies
  • 22. Monoclonal antibodies: use as a diagnostic tool
  • 23. Immunotherapy of tumors active immunotherapy passive immunotherapy non- specific BCG, Propionibacterium acne, levamisole, etc. killed tumor cells, purified or recombinant Ag specific LAK cells, cytokines non-specific antibodies alone or conjugated with other agent, activated T cells specific
  • 24. Non-specific immunotherapy activate macrophages and NK cells IFN-  , IFN-  , IFN-  , IL-2, TNF-  cytokines interferon production pyran, poly I:C synthetic molecules activate macrophages and NK cells (via cytokines) BCG, P. acnes , muramyl dipeptide bacterial products
  • 25. Cytokine immunotherapy increased expression of class-I MHC, possible anti tumor effect remission of hairy cell leukemia, weak effect on carcinomas IFN-  , -  IFN-  increased expression of class-I MHC, Tc and NK cell activation remission of ovarian carcinoma IL-2 T cell proliferation and activation, NK cell activation remission in renal cell carcinoma and melanoma TNF-  macrophage and lymphocyte activation reduction in malignant ascites
  • 26. Genetic approaches to cancer treatment
    • Transfection with genes
      • Cytokines
      • Class I MHC
      • Co-stimulatory molecules