Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen-specific T cell responses in DTH skin tests
W J Lesterhuis, I J M de Vries, D H Schuurhuis, A C I Boullart, J F M Jacobs, A J de Boer, N M Scharenborg, H M H Brouwer, M W M M van de Rakt, C G Figdor, T J Ruers, G J Adema, C J A Punt, W J Lesterhuis, I J M de Vries, D H Schuurhuis, A C I Boullart, J F M Jacobs, A J de Boer, N M Scharenborg, H M H Brouwer, M W M M van de Rakt, C G Figdor, T J Ruers, G J Adema, C J A Punt
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.
Source: PubMed