Cytotoxic T lymphocyte therapy of cancer and tumor escape mechanisms.
In animal models complete and permanent eradication of tumors can be achieved by adoptive transfer of tumor specific T cells, combined with interleukin 2. The most active cells are CD8+ cytotoxic T lymphocytes (CTL), which recognize peptides of 8-10 amino acids in length, bound to the antigen presenting groove of MHC class I molecules. In the case of virus-induced tumors these peptides are processed from viral proteins. Potentially immunogenic human tumors include melanoma and renal cell carcinoma in addition to the virus-associated cancers Burkitt's lymphoma and cervical carcinoma. The potential of CTL therapy of human cancer needs to be tested with cloned tumor cells. Remedies to over-come poor immunogenicity and evasion by tumor cells of CTL mediated-destruction are discussed.
Melief
C J
CJ
Division of Immunology, The Netherlands Cancer Institute, Amsterdam.
Kast
W M
WM
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007155:Immunologic Factors / Q000627:therapeutic use; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000637:transplantation*; D014611:Vaccination
D000951:Antigens, Neoplasm; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007155:Immunologic Factors; D007376:Interleukin-2; D010446:Peptide Fragments; D007371:Interferon-gamma