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Abstract：
T-cell receptor-engineered T-cell therapy and chimeric antigen receptor T-cell therapy are 2 types of adoptive T-cell therapy that genetically modify natural T cells to treat cancers. Although chimeric antigen receptor T-cell therapy has yielded remarkable efficacy for hematological malignancies of the B-cell lineages, most solid tumors fail to respond significantly to chimeric antigen receptor T cells. T-cell receptor-engineered T-cell therapy, on the other hand, has shown unprecedented promise in treating solid tumors and has attracted growing interest. In order to create an unbiased, comprehensive, and scientific report for this fast-moving field, we carefully analyzed all 84 clinical trials using T-cell receptor-engineered T-cell therapy and downloaded from ClinicalTrials.gov updated by June 11, 2018. Informative features and trends were observed in these clinical trials. The number of trials initiated each year is increasing as expected, but an interesting pattern is observed. NY-ESO-1, as the most targeted antigen type, is the target of 31 clinical trials; melanoma is the most targeted cancer type and is the target of 33 clinical trials. Novel antigens and underrepresented cancers remain to be targeted in future studies and clinical trials. Unlike chimeric antigen receptor T-cell therapy, only about 16% of the 84 clinical trials target against hematological malignancies, consistent with T-cell receptor-engineered T-cell therapy\'s high potential for solid tumors. Six pharma/biotech companies with novel T-cell receptor-engineered T-cell ideas and products were examined in this review. Multiple approaches have been utilized in these companies to increase the T-cell receptor\'s affinity and efficiency and to minimize cross-reactivity. The major challenges in the development of the T-cell receptor-engineered T-cell therapy due to tumor microenvironment were also discussed here.
摘要：
T细胞受体工程化T细胞疗法和嵌合抗原受体T细胞疗法是2种类型的过继性T细胞疗法,其遗传修饰天然T细胞以治疗癌症。尽管嵌合抗原受体T细胞疗法对B细胞系的血液系统恶性肿瘤产生了显着疗效，大多数实体瘤对嵌合抗原受体T细胞无明显反应。T细胞受体工程化T细胞疗法,另一方面,在治疗实体肿瘤方面显示出前所未有的希望，并吸引了越来越多的兴趣。为了创造一个不偏不倚的，全面,以及这个快速发展的领域的科学报告，我们仔细分析了所有84项使用T细胞受体工程化T细胞疗法的临床试验,并在2018年6月11日前从ClinicalTrials.gov下载.在这些临床试验中观察到了信息特征和趋势。每年启动的试验数量如预期的一样增加,但是观察到一个有趣的模式。NY-ESO-1，作为最靶向的抗原类型，是31项临床试验的目标；黑色素瘤是最有针对性的癌症类型，是33项临床试验的目标。在未来的研究和临床试验中，新的抗原和代表性不足的癌症仍有待研究。与嵌合抗原受体T细胞疗法不同，84项临床试验中只有约16%针对血液系统恶性肿瘤，与T细胞受体工程T细胞治疗实体瘤的高潜力一致。在这篇综述中，研究了六家具有新型T细胞受体工程T细胞思想和产品的制药/生物技术公司。在这些公司中已经使用了多种方法来增加T细胞受体的亲和力和效率并最小化交叉反应性。本文还讨论了由于肿瘤微环境导致的T细胞受体工程化T细胞治疗发展的主要挑战。
