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.
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 cancerpatients. 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 cancerpatients. 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.
Authors: W Joost Lesterhuis; Cornelis J A Punt; Stanleyson V Hato; Dagmar Eleveld-Trancikova; Bastiaan J H Jansen; Stefan Nierkens; Gerty Schreibelt; Annemiek de Boer; Carla M L Van Herpen; Johannes H Kaanders; Johan H J M van Krieken; Gosse J Adema; Carl G Figdor; I Jolanda M de Vries Journal: J Clin Invest Date: 2011-07-18 Impact factor: 14.808
Authors: Osama E Rahma; Ed Ashtar; Malgorzata Czystowska; Marta E Szajnik; Eva Wieckowski; Sarah Bernstein; Vincent E Herrin; Mortada A Shams; Seth M Steinberg; Maria Merino; William Gooding; Carmen Visus; Albert B Deleo; Judith K Wolf; Jeffrey G Bell; Jay A Berzofsky; Theresa L Whiteside; Samir N Khleif Journal: Cancer Immunol Immunother Date: 2011-09-17 Impact factor: 6.968