A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients

Br J Cancer. 2010 Oct 26;103(9):1415-21. doi: 10.1038/sj.bjc.6605935. Epub 2010 Oct 5.

Abstract

Background: Dendritic cell (DC) vaccination has been shown to induce anti-tumour immune responses in cancer patients, but so far its clinical efficacy is limited. Recent evidence supports an immunogenic effect of cytotoxic chemotherapy. Pre-clinical data indicate that the combination of chemotherapy and immunotherapy may result in an enhanced anti-cancer activity. Most studies have focused on the immunogenic aspect of chemotherapy-induced cell death, but only few studies have investigated the effect of chemotherapeutic agents on the effector lymphocytes of the immune system.

Methods: Here we investigated the effect of treatment with oxaliplatin and capecitabine on non-specific and specific DC vaccine-induced adaptive immune responses. Stage III colon cancer patients receiving standard adjuvant oxaliplatin/capecitabine chemotherapy were vaccinated at the same time with keyhole limpet haemocyanin (KLH) and carcinoembryonic antigen (CEA)-peptide pulsed DCs.

Results: In 4 out of 7 patients, functional CEA-specific T-cell responses were found at delayed type hypersensitivity (DTH) skin testing. In addition, we observed an enhanced non-specific T-cell reactivity upon oxaliplatin administration. KLH-specific T-cell responses remained unaffected by the chemotherapy, whereas B-cell responses were diminished.

Conclusion: The results strongly support further testing of the combined use of specific anti-tumour vaccination with oxaliplatin-based chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibody Formation
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • B-Lymphocytes / immunology
  • Cancer Vaccines / administration & dosage*
  • Capecitabine
  • Chemotherapy, Adjuvant
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / immunology*
  • Dendritic Cells / immunology*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives*
  • Humans
  • Hypersensitivity, Delayed / etiology
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage*
  • Oxaliplatin
  • Pilot Projects
  • T-Lymphocytes / immunology*

Substances

  • Cancer Vaccines
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • Capecitabine
  • Fluorouracil