P21-RAS-PEPTIDE-SPECIFIC T-CELL RESPONSES IN A PATIENT WITH COLORECTAL-CANCER - CD4(-CELLS RECOGNIZE A PEPTIDE CORRESPONDING TO A COMMON MUTATION (13 GLY-]ASP)() AND CD8(+) T)

Peptides derived from mutated ras are immunogenic in ice and humans, a nd represent a group of specific tumor antigens that are potential tar gets for immunotherapy. T-cell responses against mutant p21 ras can be initiated in vitro by repeated stimulation of peripheral-blood mononu clear cells with mutant ras-derived peptides. Patients with tumors com monly harbouring ras mutations may therefore show evidence of in vivo reactivity against such mutations. Peripheral-blood mono-nuclear cells from 10 patients with colorectal adenocarcinoma were screened for rea ctivity against synthetic ras-derived peptides corresponding to the mo st commonly found mutations in this type of cancer. In one patient, T- cell reactivity against the 1-25,13Gly-->Asp peptide was detected. Fro m this patient, both CD4(+) and CD8(+) T-cell clones specific for the 1-25,13Gly-->Asp mutation in the ras oncogene is frequent and constitu tes 9 to 27% of all K ras mutations found in biopsies from patients wi th colorectal carcinomas. Our study demonstrates a mutant ras-specific T-cell response of both the CD4(+) and the CD8(+) phenotype in a canc er patient. We speculate that in this patient a specific T-cell respon se resulted in eradication of tumor cells harboring the 13Gly-->Asp mu tation.