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. © 1994 Wiley‐Liss, Inc.