Targeting p53 as a general tumor antigen.
A major barrier to the design of immunotherapeutics and vaccines for cancer is the idiosyncratic nature of many tumor antigens and the possibility that T cells may be tolerant of broadly distributed antigens. We have devised an experimental strategy that exploits species differences in protein sequences to circumvent tolerance of high-affinity T cells. HLA transgenic mice were used to obtain cytotoxic T lymphocytes specific for peptides from the human p53 tumor-suppressor molecule presented in association with HLA-A2.1. Although such p53-specific cytotoxic T cells did not recognize nontransformed human cells, they were able to lyse a wide variety of human tumor cells lines, thus confirming the existence of broadly distributed determinants that may serve as targets for immunotherapy.
Theobald
M
M
Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Biggs
J
J
Dittmer
D
D
Levine
A J
AJ
Sherman
L A
LA
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015789:HLA-A2 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000276:immunology*; D014614:Vaccines, Synthetic
D000951:Antigens, Neoplasm; D000939:Epitopes; D015789:HLA-A2 Antigen; D009842:Oligopeptides; D016159:Tumor Suppressor Protein p53; D014614:Vaccines, Synthetic