Anti-tumor immune response induced by necrotic tumor cell vaccines

• Main Authors: Chi Wei Lin, 林志偉
• Other Authors: Kai Ping Chow
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/75055817179825849308

碩士 === 長庚大學 === 基礎醫學研究所 === 92 === In recent years, evidences have been accumulated that substances released from freeze and thaw (FT) necrotic tumor cells can stimulate anti-tumor immunity through dendritic cells. However, no effective protection was demonstrated with the injection of FT-treated whole tumor necrotic cells. To mimic the necrosis generated in vivo, here, we focused the effectiveness of whole necrotic cell as vaccine by using photofrin, a photochem-therapeutic agent-treated melanoma B16F10 cells in the induction of anti-tumor immunity. After activated by laser, photofrin has been known to exert its therapeutic effect mainly through induction of necrosis. Tumor cell lysate generated from photofrin and laser (PL) treatment has been reported to be more effective in turns of vaccine effectiveness than FT-treated tumor cell lysate. Therefore, this study is focused on whether PL-treated whole necrotic B16F10 can by itself induce anti-tumor immunity in B6 mice system. First, we provide evidences that the cell underwent typical necrosis after PL treatment. Next, we examined the effectiveness of PL-treated whole necrotic tumor cell vaccine, in comparison with FT treatment, by direct subcutaneous injection. While all the mice received FT vaccine failed to protect host from tumor development, PL vaccine induces anti-tumor immunity effectively. In the in vivo antibody depletion experiment, the immunity was found dependent upon both NK and CD4 T cells. By flow cytometry, we analyzed the change of cell type, cell activation state, as well as the cytokine secretion in the draining lymph node (DLN). In result, both PL and FT groups induced NK, macrophage and T cell activation on day 1-8. However, only PL group exerted a second wave of response on day 12. By further analysis, a subset of dendritic cells bearing F4/80 was found consistently appeared on day 5 to day 12 in PL group. In conclusion, our data suggested that PF-treated whole melanoma necrotic cells can induce anti-tumor immunity by generation of more active and persistent effector-APC interaction.