Vaccination with autologous tumor-derived heat-shock protein gp96 after liver resection for metastatic colorectal cancer

Clin Cancer Res. 2003 Aug 15;9(9):3235-45.


Purpose: Heat shock proteins (HSP) from tumor cells contain the gp96 polypeptide associated with cancer-specific antigenic peptides. Mice that are immunized with HSP/peptide-complex (HSPPC) derived from cancer tissue reject tumor from which HSPs are purified. We tested in humans whether vaccination with HSPPC-gp96 (Oncophage) from autologous liver metastases of colorectal carcinoma induces cancer-specific T-cell responses in patients rendered disease free by surgery.

Experimental design: Twenty-nine consecutive patients underwent radical resection of liver metastases [Memorial Sloan-Kettering Cancer Center (MSKCC) score 1-3 (good prognosis), 18 patients; score 4-5 (bad prognosis), 11 patients] and received autologous tumor-derived HSPPC-96. Two vaccine cycles were administered (four weekly injections followed by four biweekly injections after 8 weeks). Class-I HLA-restricted, anti-colon cancer lines T-cell response was measured by ELISPOT assay on peripheral blood mononuclear cells (PBMCs) obtained before and after vaccination. Feasibility, safety, and possible clinical benefits were also evaluated.

Results: Either a de novo induced or a significant increase of preexisting class I HLA-restricted T-cell-mediated anti-colon cancer response was observed in 15 (52%) of 29 patients. Frequency of CD3+, CD45RA+, and CCR7- T lymphocytes increased in immune responders. No relevant toxicity was observed. As expected, patients with good prognosis had a significantly better clinical outcome than those with poor prognosis [2-year overall survival (OS), 89 versus 64%, P = 0.001; disease-free survival (DFS), 46 versus 18%, P = 0.001]. Patients with immune response had a statistically significant clinical advantage over nonresponding subjects (2-year OS, 100% versus 50%, P = 0.001; DFS, 51% versus 8%, P = 0.0001). Occurrence of immune response led to better tumor-free survival, whatever the predicted prognosis was (hazard ratio, 0.11-0.12 with/without stratification; P = 0.0012-0.0003).

Conclusions: HSPPC-96 vaccination after resection of colorectal liver metastases is safe and elicits a significant increase in CD8+ T-cell response against colon cancer. In this limited number of patients, two-year OS and DFS were significantly improved in subjects with postvaccination antitumor immune response, independently from other clinical prognostic factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / chemistry*
  • Antigens, Neoplasm / genetics*
  • CD3 Complex / biosynthesis
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / chemistry
  • Cohort Studies
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery*
  • Colorectal Neoplasms / therapy*
  • Disease-Free Survival
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Histocompatibility Testing
  • Humans
  • Immunophenotyping
  • Leukocyte Common Antigens / biosynthesis
  • Leukocytes, Mononuclear / metabolism
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Peptides / chemistry
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Receptors, CCR7
  • Receptors, Chemokine / biosynthesis
  • Regression Analysis
  • T-Lymphocytes / metabolism
  • Treatment Outcome


  • Antigens, Neoplasm
  • CCR7 protein, human
  • CD3 Complex
  • Cancer Vaccines
  • Peptides
  • Receptors, CCR7
  • Receptors, Chemokine
  • sarcoma glycoprotein gp96 rejection antigens
  • Leukocyte Common Antigens