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)

✍ Scribed by Beate Fossum; Tobias Gedde-Dahl III; Jarle Breivik; Jon Amund Eriksen; Anne Spurkland; Erik Thorsby; Gustav Gaudernack

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: French
• Weight: 979 KB
• Volume: 56
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910560108

✦ Synopsis

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 p2I 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, I3Gly+Asp peptide was detected. From this patient, both CD4+ and CD8+ T-cell clones specific for the 1-25. I3Gly+Asp mutation could be raised. We were not, however, able to detect the corresponding mutation in the cancer. The I3Gly+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 rasspecific 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 I3Gly+Asp mutation.