Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma

K-RAS mutations are frequently found in adenocarcinomas of the pancreas, an d induction of immunity against mutant ras can therefore be of possible cli nical benefit in patients with pancreatic cancer. We present data from a cl inical phase I/II trial involving patients with adenocarcinoma of the pancr eas vaccinated by i.d. injection of synthetic mutant ras peptides in combin ation with granulocyte-macrophage colony-stimulating Factor. Forty-eight pa tients(10 surgically resected and 38 with advanced disease) were treated on an outpatient basis. Peptide-specific immunity was induced in 25 of 43 (58 %) evaluable patients, indicating that the protocol used is very potent and capable of eliciting immune responses even in patients with end-stage dise ase. Patients followed-up for longer periods showed evidence of induction o f long-lived immunological memory against the ras mutations. CD4(+) T cells reactive with an Arg12 mutation also present in the tumor could be isolate d from a tumor biopsy, demonstrating that activated, ras-specific T cells w ere able to selectively accumulate in the tumor. Vaccination was well toler ated in all patients, Patients with advanced cancer demonstrating an immune response to the peptide vaccine showed prolonged survival from the start o f treatment compared to non-responders (median survival 148 days vs, 61 day s, respectively; P = 0.0002), Although a limited number of patients were in cluded in our study, the association between prolonged survival and an immu ne response against the vaccine suggests that a clinical benefit of ras pep tide vaccination may be obtained for this group of patients. (C) 2001 Wiley -Liss, Inc.