Immunotherapeutic role of mutant ras peptide-based vaccine as an adjuvant in pancreatic and colorectal cancer

Abstract

2573 Background: The ras oncogene is one of the best characterized oncogenes in human cancers; it is frequently mutated by a single amino acid substitution of codon 12. Those mutations are prevalent in many types of cancer including pancreatic adenocarcinoma (∼90%), colorectal adenocarcinoma (∼50%), and are associated with the malignant transformation and production of proteins that are unique for cancer cells. Methods: in a previous phase I study we concluded that a dose up to 5000 micrograms of peptide reflecting the patient mutant ras was well tolerated. Same dose was used in this phase II clinical trial were 12 cancer patients (5 fully resected pancreatic and 7 Dukes C or D colorectal) were vaccinated subcutaneously with the 13 mer mutant ras peptide, corresponding to their tumor’s ras mutation, admixed with DETOXTM adjuvant. Vaccinations are given every four weeks, up to total six cycles. Results: We didn’t see any serious systemic side effects and no delayed toxicities have occurred to date. We detected specific immune response to the relevant mutant ras peptide by measuring IFN-gamma mRNA expression by Quantitative real-time PCR. Five out of eleven patients showed a 1.5 folds or more increase in IFN-gamma copies accumulation in PBMCs after 3 cycles of vaccination. Furthermore, the 5 pancreatic cancer patients have shown a mean Disease-Free Survival (DFS) of 35.2+ months and a mean Post-Vaccination Survival (PVS) of 44.4+ months. The 7 colorectal patients have shown a mean Disease-Free Survival (DFS) of 27.2+ months and a mean Post-Vaccination Survival of 41.5+ months. Conclusions: mutant ras is an attractive target for vaccine therapy of cancer patients who carry the ras mutation in their cancer and it warrants further investigations No significant financial relationships to disclose.