Establisment of tumor vaccine using autologous dendritic cells and its application for addaptive immunotherapy

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Dendritic cells (DC) possess the most potent antigen-prersenting activity among various antigen presenting cells. This study aims preclinical application of tumor vaccine using autologous dendritic cells. We tried to establish autologous dendritic cell vaccine using autologous colon cancer cells and dendritic cells, and focused on investigation of the methods for effective induction of autolpogpus tumor spesific T cells and culture system for tumor-spesific dendritic cells. We first established colon carcinoma cell line, CE-1, from the 38 years. male patient with advanced colon cancer. These tumor cells revealed HLA-type Class I A31, and A11. We tried to establish tumor-spesific adendritic cells using autologouis cells and HLA-matched healthy volunteer. 1-2 x 10^6 dendritic cells were obtained from 100 ml of heparinized peripheral blood and culture media containing IL-4 and GM-CSF.When irradiated or freezing-thawing tumor cells were added to the dendritic cells and furtherly cultured in the presence of IL-4 and GM-CS F, tumor-spesific dendritic cells were obtained. These cells were positive for expression of IL-12 and IFN-gamma mRNA and the expression of HLA-DR, CD80, and ICAM-1.When autologous T cells were added to the tumor-pulsed dendritic cells and cultured in the presence of IL-2 and IL-4 for subsequent 2 weeks, autologous tumor-reactive CTL were obtained. Because theses T cell possess cytotoxic activity against autologous tumor cells releasing IFN-gamma. However we failed in culture of dendritic cells in a large number using gellatin-beads, which was one of aims of this study. Further studies are needed to establish and verify effective systems for culture of autologpus-tumor pulsed dendritic cell vaccine.