VACCINATION WITH MUTANT RAS PEPTIDES AND INDUCTION OF T-CELL RESPONSIVENESS IN PANCREATIC-CARCINOMA PATIENTS CARRYING THE CORRESPONDING RASMUTATION

Mutations in codon 12 of K-RAS are frequently found in pancreatic aden ocarcinomas. T-cell responses specific for individual RAS mutations ca n be elicited in vitro by stimulation of peripheral blood mononuclear cells with synthetic peptides. Mutant ras peptides are therefore a can didate vaccine for specific immunotherapy in pancreatic carcinoma pati ents. When vaccinated with a synthetic ras peptide representing the K- RAS mutation in their tumours, a transient ras-specific T-cell respons e was induced in two of five patients treated. The vaccination protoco l involved multiple in fusions of large amounts of peptide-pulsed anti gen-presenting-cells obtained by leucapheresis. These results indicate that specific T-cell responses against mutations uniquely harboured i n tumour cells can be induced in cancer patients by vaccination.