Immunotherapy by intratumoral administration of dendritic cells following cryoablative tumor treatment

• Published in: Nihon Rinsho Men'eki Gakkai Sokai Shorokushu Vol. 36; p. 11
• Main Authors: 斉藤, 昌孝, 桜井, 敏晴, 半田, 誠, 天谷, 雅行, 北島, 政樹, 北川, 雄光, 泉, 陽太郎, 谷川, 瑛子, 河上, 裕, 宇田川, 勝, 谷口, 智憲, 工藤, 千恵, 田辺, 稔, 藤田, 知信, 石田, 明, 川村, 雅文, 東, 一郎, 住本, 秀敏, 小林, 紘一
• Format: Journal Article
• Language: Japanese
• Published: 日本臨床免疫学会 2008; The Japan Society for Clinical Immunology
• Subjects: Cancer; Dendritic Cell; Immunotherapy
• ISSN: 1880-3296
• DOI: 10.14906/jscisho.36.0.11.0

Our previous studies on immune response to tumor antigens indicated importance of individualization for immunotherapy. We developed individualized immunotherapy by intratumoral (i.t.) administration of dendritic cells (DC), in combination with cryoablative tumor pretreatment and DC stimulation with TLR activating BCG-CWS. The enhanced uptake of tumor antigens by the injected DC through cryoablation induced tumor cell necrosis, and the BCG-CWS induced DC maturation, enhanced systemic induction of anti-tumor CD8+ CTL, resulting in regression of relatively large untreated remote tumors in murine model. Additional treatments, including regulatory T cell inhibition or immunogenic antigen pulsing on DC, further enhanced the anti-tumor effects through enhanced antigen spreading. Clinical trials were conducted for various cancer patients. Although SD with decreased tumor marker was obtained in some patients along with induction of systemic immune responses, anti-tumor effects were weak. Additional improvements, including tumor debulking, injection of more tumor antigen pulsed DC, and inhibition of tumor induced immunosuppression, appear to be required for more effective immunotherapy.