Cancer immunotherapy using gene-engineered T cells
Cancer immunotherapy using gene-engineered T cells
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使用基因工程 T 细胞进行癌症免疫治疗
DOI：
10.11406/rinketsu.59.216
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
影山 愼一
中科院分区：
文献类型：
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作者：
Imaoka H;Toiyama Y;Okigami M;Yasuda H;Saigusa S;Ohi M;Tanaka K;Inoue Y;Mohri Y;Kusunoki M;庄田勝俊 市川大輔 岡本和真;奥川 喜永;影山 愼一
使用基因工程T细胞的癌症免疫治疗包括过继转移T细胞受体(TCR)和嵌合抗原受体(CAR)基因转导的T细胞。CD19靶向的CAR-T细胞治疗是目前治疗B细胞肿瘤最有效的方法，但它也会引起细胞因子释放综合征和神经毒性，常常导致严重的不良反应。值得注意的是，TCR-T细胞治疗主要用于靶向黑色素瘤，导致30%-50%的肿瘤反应。在针对NY-ESO-1表达的滑膜肉瘤的临床试验中，已经获得了50%-60%的高有效率。到目前为止，还没有关于上皮性肿瘤的具体临床疗效的报道。据报道，在正常组织中使用亲和力增强的突变或小鼠来源的TCR时，会产生严重的靶向不良反应。此外，使用高亲和力的TCR和靶向可能在正常组织中表达的肿瘤抗原也存在潜在的风险。
Cancer immunotherapies using gene-engineered T cells comprise adoptive transfer of T-cell receptor (TCR) and chimeric antigen receptor (CAR) gene-transduced T cells. Although CD19-targeting CAR-T cell therapy is the most progressed, wherein B-cell malignancy is treated efficiently, it also induces cytokine release syndrome and neurotoxicity, which frequently leads to serious adverse events. Of note, TCR-T cell therapy has been primarily used to target melanoma, resulting in 30%-50% of tumor responses. In clinical trials that target NY-ESO-1-expressing synovial sarcoma, a high efficacy of 50%-60% has been obtained. To date, no specific clinical efficacy has been reported for epithelial tumors. Serious on-target adverse effects in normal tissues have been reported when using affinity-enhanced TCR of mutated or mouse-derived ones. Furthermore, there are potential risks in using high-affinity TCRs and in targeting tumor antigens that may also be expressed in normal tissues.