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Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study
Authors:Hirohito Kobayashi  Yoshimasa Tanaka  Junji Yagi  Yukinari Osaka  Hayakazu Nakazawa  Takehiko Uchiyama  Nagahiro Minato  Hiroshi Toma
Affiliation:(1) Department of Urology, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan;(2) Department of Urology, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan;(3) Laboratory of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan;(4) Department of Microbiology and Immunology, Tokyo Women’s Medical University, Tokyo, Japan
Abstract:Purpose Although various types of immunotherapy have been used to improve the prognosis of patients with advanced renal cell carcinoma (RCC), adoptive immunotherapy using gamma-delta (γδ) T cells has not yet been tried. In this study, we designed a pilot study of adoptive immunotherapy using in vitro activated γδ T cells against advanced RCC to evaluate the safety profile and possible anti-tumor effects of this study. Experimental design Patients with advanced RCC after radical nephrectomy were administered via intravenous infusion in vitro-activated autologous γδ T cells every week or every 2 weeks, 6–12 times, with 70 JRU of teceleukin. Adverse events, anti-tumor effects and immunomonitoring were assessed. The anti-tumor effects were evaluated according to tumor doubling time (DT) by computed tomography (CT) and immunomonitoring was performed by flow cytometric analysis. Results Seven advanced RCC patients were entered in this study. The most common adverse events were fever, general fatigue and elevation of hepatobiliary enzymes, but no severe adverse events were seen. Prolongation of tumor DT was seen in three out of five patients; these three patients showed an increase in the number of γδ T cells in peripheral blood and also a high response to the antigen in vitro. Conclusions The results indicated that adoptive immunotherapy using in vitro-activated autologous γδ T cells was well tolerated and induced anti-tumor effects.
Keywords:Renal cell carcinoma  Adoptive immunotherapy  Gamma-delta T cell  Pilot study
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