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.