がん治療・がん免疫療法「癌樹状細胞療法」のセレンクリニック／リンク集

Immunotherapy of Murine Malignant Mesothelioma Using Tumor Lysate-pulsed Dendritic Cells

Joost P. J. J. Hegmans et al.

American Journal Of Respiratory And Critical Care Medicine Vol.171, 1168-1177, (2005).

Rationale: Exploiting the immunostimulatory capacities of dendriticcells holds great promise for cancer immunotherapy. Currently,dendritic cell-based immunotherapy is evaluated clinicallyin a number of malignancies, including melanoma and urogenitaland lung cancer, showing variable but promising results. Objective:To evaluate if pulsed dendritic cells induce protective immunityagainst malignant mesothelioma in a mouse model. Methods: Malignantmesothelioma was induced in mice by intraperitoneal injectionof the AB1 mesothelioma cell line, leading to death within 28days. For immunotherapy, dendritic cells were pulsed overnighteither with AB1 tumor cell line lysate, AB1-derived exosomes,or ex vivo AB1 tumor lysate, and injected either before (Days-14 and -7) at the day of (Day 0) or after (Days+1 and +8) tumor implantation. Main Results: Mice receivingtumor lysate-pulsed dendritic cells before tumor implantationdemonstrated protective antitumor immunity with prolonged survival(> 3 months) and even resisted secondary tumor challenge. Tumorprotection was associated with strong tumor-specific cytotoxicT-lymphocyte responses. Adoptive transfer of splenocytes orpurified CD8+ T lymphocytes transferred tumor protection tounimmunized mice in vivo. When given after tumor implantationin a therapeutic setting, pulsed dendritic cells prevented mesotheliomaoutgrowth. With higher tumor load and delayed administrationafter tumor implantation, dendritic cells were no longer effective. Conclusions: We demonstrate in this murine model that immunotherapyusing pulsed dendritic cells may emerge as a powerful tool tocontrol mesothelioma outgrowth. In the future, immunotherapyusing dendritic cells could be used as adjuvant to control localrecurrence after multimodality treatment for malignant mesotheliom.