Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific T cell responses in DTH skin tests

Ann Oncol. 2006 Jun;17(6):974-80. doi: 10.1093/annonc/mdl072. Epub 2006 Apr 6.

Abstract

Background: Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. As such they are currently used in clinical vaccination protocols in cancer patients.

Patients and methods: We evaluated the ability of mature DCs pulsed with carcinoembryonic antigen (CEA)-peptide to induce CEA-specific T cell responses in patients with resectable liver metastases from colorectal cancer. CEA-specific T cell reactivity was monitored in peripheral blood, biopsies of vaccination sites and post-treatment DTH skin tests, and when available also in resected abdominal lymph nodes and tumor tissue.

Results: Ten patients were vaccinated intradermally and intravenously with CEA-peptide pulsed mature DCs three times prior to resection of liver metastases. High numbers of CEA-specific T cells were detected in post-treatment DTH biopsies in seven out of 10 patients, which produced high amounts of interferon (IFN)-gamma upon stimulation with CEA-loaded target cells. These responses were not found in biopsies of first vaccination sites, indicating a de novo T cell induction or at least a strong potentiation by the vaccine. In addition, CEA-specific T cells were detected in a resected lymph node in one patient, but not in peripheral blood or tumor tissue.

Conclusions: Vaccination with CEA-peptide loaded mature DCs induced potent CEA-specific T cell responses in advanced colorectal cancer patients. In this study, antigen-specific T cell responses were readily detected in DTH skin tests, much less in abdominal lymph nodes, and not in peripheral blood and tumor tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cancer Vaccines* / administration & dosage
  • Carcinoembryonic Antigen / immunology*
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / pathology
  • Dendritic Cells / transplantation*
  • Drug Administration Schedule
  • Humans
  • Hypersensitivity, Delayed / immunology*
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / surgery
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Lymphocyte Activation
  • Monitoring, Immunologic
  • Patient Selection
  • Skin Tests
  • T-Lymphocytes / immunology*
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Cancer Vaccines
  • Carcinoembryonic Antigen