p21-ras-peptide-specific T-cell responses in a patient with colorectal cancer. CD4+ and CD8+ T cells recognize a peptide corresponding to a common mutation (13Gly-->Asp).
Peptides derived from mutated ras are immunogenic in mice and humans, and represent a group of specific tumor antigens that are potential targets for immunotherapy. T-cell responses against mutant p21 ras can be initiated in vitro by repeated stimulation of peripheral-blood mononuclear cells with mutant ras-derived peptides. Patients with tumors commonly harbouring ras mutations may therefore show evidence of in vivo reactivity against such mutations. Peripheral-blood mononuclear cells from 10 patients with colorectal adenocarcinoma were screened for reactivity against synthetic ras-derived peptides corresponding to the most commonly found mutations in this type of cancer. In one patient, T-cell reactivity against the 1-25,13Gly-->Asp peptide was detected. From this patient, both CD4+ and CD8+ T-cell clones specific for the 1-25,13Gly-->Asp mutation could be raised. We were not, however, able to detect the corresponding mutation in the cancer. The 13Gly-->Asp mutation in the ras oncogene is frequent and constitutes 9 to 27% of all K ras mutations found in biopsies from patients with colorectal carcinomas. Our study demonstrates a mutant ras-specific T-cell response of both the CD4+ and the CD8+ phenotype in a cancer patient. We speculate that in this patient a specific T-cell response resulted in eradication of tumor cells harboring the 13Gly-->Asp mutation.
Fossum
B
B
Institute of Transplantation Immunology, National Hospital, University of Oslo, Norway.
Gedde-Dahl
T
T
Breivik
J
J
Eriksen
J A
JA
Spurkland
A
A
Thorsby
E
E
Gaudernack
G
G
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D001224:Aspartic Acid / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured / Q000276:immunology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology*; D005260:Female; D005784:Gene Amplification; D011905:Genes, ras / Q000235:genetics / Q000276:immunology; D005998:Glycine / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D010641:Phenotype; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016827:CD8 Antigens; D010455:Peptides; D001224:Aspartic Acid; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D005998:Glycine