嵌合抗原受体
MUC1号
癌症研究
抗原
T细胞
单链可变片段
医学
肿瘤抗原
癌症
免疫疗法
免疫学
免疫系统
抗体
内科学
单克隆抗体
作者
Fengming You,Licui Jiang,Bozhen Zhang,Qiang Lü,Qiao Zhou,Xiaoyang Liao,Hong Wu,Ke Du,You‐cai Zhu,Hua Meng,Zhishu Gong,Yunhui Zong,Lei Huang,Man Lu,Jirong Tang,Yafen Li,Xiaochen Zhai,Xiangling Wang,Sisi Ye,Dan Chen,Lei Yuan,Qian Lin,Lin Yang
标识
DOI:10.1007/s11427-016-5024-7
摘要
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.
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