Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells
Phase 1 clinical trial demonstrated that MUC1 positive metastatic seminal vesicle cancer can be effectively eradicated by modified Anti-MUC1 chimeric antigen receptor transduced T cells
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一期临床试验表明，改良的抗MUC1嵌合抗原受体转导的T细胞可以有效根除MUC1阳性转移性精囊癌
DOI：
10.1007/s11427-016-5024-7
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发表时间：
2016-04-01
影响因子：
9.1
通讯作者：
Yang, Lin
中科院分区：
文献类型：
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作者：
You, Fengtao;Jiang, Licui;Yang, Lin
嵌合抗原受体修饰的t细胞（CAR-T细胞）技术在癌症治疗中的最新进展非常有前景，特别是在治疗b细胞急性淋巴细胞白血病患者方面。相比之下，由于实体肿瘤的敌对免疫抑制微环境，CAR - t细胞的可及性和存活率继续构成相当大的挑战，这导致它们的治疗效果有限。在本研究中，我们构建了两个抗muc1 CAR-T细胞系。一组CAR-T细胞含有特异性靶向MUC1抗原并共表达白细胞介素（IL） 12的SM3单链可变片段（scFv）序列（命名为SM3- car）。另一种CAR-T细胞系携带经过修饰的SM3 scFv序列以改善其与MUC1抗原的结合（命名为pSM3-CAR），但不共表达IL-12。当将这两种类型的CAR-T细胞作为介入治疗策略的一部分，注射到同一名MUC1（+）精囊癌患者的两个独立转移灶时，初步结果表明，MUC1靶向CAR-T细胞方法没有副作用，患者血清细胞因子反应呈阳性。进一步的评价表明pSM3-CAR能有效地引起肿瘤坏死，为实体瘤改良CAR-T治疗提供了新的选择。
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.