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

Int J Cancer. 2001 May 1;92(3):441-50. doi: 10.1002/ijc.1205.


K-RAS mutations are frequently found in adenocarcinomas of the pancreas, and induction of immunity against mutant ras can therefore be of possible clinical benefit in patients with pancreatic cancer. We present data from a clinical phase I/II trial involving patients with adenocarcinoma of the pancreas vaccinated by i.d. injection of synthetic mutant ras peptides in combination with granulocyte-macrophage colony-stimulating factor. Forty-eight patients (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 disease. Patients followed-up for longer periods showed evidence of induction of long-lived immunological memory against the ras mutations. CD4(+) T cells reactive with an Arg12 mutation also present in the tumor could be isolated from a tumor biopsy, demonstrating that activated, ras-specific T cells were able to selectively accumulate in the tumor. Vaccination was well tolerated in all patients. Patients with advanced cancer demonstrating an immune response to the peptide vaccine showed prolonged survival from the start of treatment compared to non-responders (median survival 148 days vs. 61 days, respectively; p = 0.0002). Although a limited number of patients were included in our study, the association between prolonged survival and an immune response against the vaccine suggests that a clinical benefit of ras peptide vaccination may be obtained for this group of patients.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / mortality
  • Adenocarcinoma / prevention & control*
  • Adjuvants, Immunologic / adverse effects
  • Adjuvants, Immunologic / therapeutic use
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Hypersensitivity, Delayed / etiology
  • Injections, Intradermal
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / prevention & control*
  • Peptides / adverse effects
  • Peptides / therapeutic use
  • Survival Rate
  • T-Lymphocytes / immunology
  • Treatment Outcome
  • Vaccination
  • ras Proteins / adverse effects
  • ras Proteins / therapeutic use*


  • Adjuvants, Immunologic
  • Peptides
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • ras Proteins