Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras

Int J Cancer. 2011 Mar 1;128(5):1120-8. doi: 10.1002/ijc.25449.

Abstract

K-ras mutations are frequently found in adenocarcinomas of the pancreas and can elicit mutation-specific immune responses. Targeting the immune system against mutant Ras may thus influence the clinical course of the disease. Twenty-three patients who were vaccinated after surgical resection for pancreatic adenocarcinoma (22 pancreaticoduodenectomies, one distal resection), in two previous Phase I/II clinical trials, were followed for more than 10 years with respect to long-term immunological T-cell reactivity and survival. The vaccine was composed of long synthetic mutant ras peptides designed mainly to elicit T-helper responses. Seventeen of 20 evaluable patients (85%) responded immunologically to the vaccine. Median survival for all patients was 27.5 months and 28 months for immune responders. The 5-year survival was 22% and 29%, respectively. Strikingly, 10-year survival was 20% (four patients out of 20 evaluable) versus zero (0/87) in a cohort of nonvaccinated patient treated in the same period. Three patients mounted a memory response up to 9 years after vaccination. The present observation of long-term immune response together with 10-year survival following surgical resection indicates that K-ras vaccination may consolidate the effect of surgery and represent an adjuvant treatment option for the future.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / surgery
  • Adenocarcinoma / therapy
  • Aged
  • Cancer Vaccines / administration & dosage*
  • Female
  • Follow-Up Studies
  • Genes, ras / immunology*
  • Humans
  • Hypersensitivity, Delayed
  • Immunologic Memory
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / surgery
  • Pancreatic Neoplasms / therapy
  • Survival Analysis
  • T-Lymphocytes / immunology

Substances

  • Cancer Vaccines