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  • Phase 1 clinical trial demo...
    You, Fengtao; Jiang, Licui; Zhang, Bozhen; Lu, Qiang; Zhou, Qiao; Liao, Xiaoyang; Wu, Hong; Du, Kaiqi; Zhu, Youcai; Meng, Huimin; Gong, Zhishu; Zong, Yunhui; Huang, Lei; Lu, Man; Tang, Jirong; Li, Yafen; Zhai, Xiaochen; Wang, Xiangling; Ye, Sisi; Chen, Dan; Yuan, Lei; Qi, Lin; Yang, Lin

    Science China. Life sciences, 04/2016, Letnik: 59, Številka: 4
    Journal Article

    Recent progress in chimeric antigen receptor-modified T-cell (CAR-T cell) technology in cancer therapy is extremely promising, especially in the treatment of patients with B-cell acute lymphoblastic leukemia. In contrast, due to the hostile immunosuppressive microenvironment of a solid tumor, CAR T-cell accessibility and survival continue to pose a considerable challenge, which leads to their limited therapeutic efficacy. In this study, we constructed two anti-MUC1 CAR-T cell lines. One set of CAR-T cells contained SM3 single chain variable fragment (scFv) sequence specifically targeting the MUC1 antigen and co-expressing interleukin (IL) 12 (named SM3-CAR). The other CAR-T cell line carried the SM3 scFv sequence modified to improve its binding to MUC1 antigen (named pSM3-CAR) but did not co-express IL-12. When those two types of CAR-T cells were injected intratumorally into two independent metastatic lesions of the same MUC1 + seminal vesicle cancer patient as part of an interventional treatment strategy, the initial results indicated no side-effects of the MUC1 targeting CAR-T cell approach, and patient serum cytokines responses were positive. Further evaluation showed that pSM3-CAR effectively caused tumor necrosis, providing new options for improved CAR-T therapy in solid tumors.