Antitumor activity of human gamma delta T cells transducted with CD8 and with T-cell receptors of tumor-specific cytotoxic T lymphocytes (Retracted article. See vol. 105, pg. 141, 2014)

作者：Hanagiri Takeshi^*; Shigematsu Yoshiki; Kuroda Koji; Baba Tetsuro; Shiota Hironobu; Ichiki Yoshinobu; Nagata Yoshika; Yasuda Manabu; So Tomoko; Takenoyama Mitsuhiro; Tanaka Fumihiro

来源：Cancer Science, 2012, 103(8): 1414-1419.

DOI：10.1111/j.1349-7006.2012.02337.x

The difficulty in the induction and preparation of a large number of autologous tumor-specific cytotoxic T lymphocytes (CTL) from individual patients is one of major problems in their application to adoptive immunotherapy. The present study tried to establish the useful antitumor effectors by using gamma delta T cells through tumor-specific TCRa beta genes transduction, and evaluated the efficacy of their adoptive transfer in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice model. The TCRa beta gene was cloned from the HLA-B15-restricted CTL clone specific of the Kita-Kyushu Lung Cancer antigen-1 (KK-LC-1). The cloned TCRa beta as well as the CD8 gene were transduced into gamma delta d T cells induced from peripheral blood lymphocytes (PBL). Cytotoxic T lymphocyte activity was examined using a standard 4 h 51Cr release assay. Mice with a xenotransplanted tumor were treated with an injection of effector cells. Successful transduction of TCRa beta was confirmed by the staining of KK-LC-1-specific tetramers. The gamma delta T cells transduced with TCR alpha beta and CD8 showed CTL activity against the KK-LC-1-positive lung cancer cell line in a HLA B15-restricted manner. Adoptive transfer of the effector cells in a mice model resulted in marked growth suppression of KK-LC-1- and HLA-B15-positive xenotransplanted tumors. Co-transducing TCRa beta and CD8 into gamma delta T cells yielded the same antigen-specific activity as an original CTL in vitro and in vivo. The TCRa beta gene transduction into gamma delta T cells is a promising strategy for developing new adoptive immunotherapy. (Cancer Sci 2012; 103: 14141419)

• 出版日期2012-8