MUTATED RAS PEPTIDES AS VACCINES IN IMMUNOTHERAPY OF CANCER

Mutations in codon 12 and 13 of K-RAS are frequently found in human ca ncer, including pancreatic- and colorectal adenocarcinomas. T cell res ponses specific for individual RAS mutations can be elicited in vitro by stimulation with synthetic peptides and in vivo following vaccinati on with antigen presenting cells pulsed ex vivo with synthetic peptide s. The peptide-responding T cells are capable of responding to intact p21 ras, and can recognise and kill tumour cell lines and isolated tum our cells harbouring the corresponding RAS mutation. The responding ce lls can be of both CD4+ and CD8+ phenotype, and these T cell subsets r ecognise nested epitopes within the vaccine peptides. Mutant ras pepti des are therefore possibly an important vaccine for specific immunothe rapy in patients with pancreatic and colorectal carcinomas, and are cu rrently being tested in vivo together with GM-CSF as an adjuvant in th ese cancer patients.