Fujiwara Hiroshi
First Department of Internal Medicine, Ehime University Hospital, Shitsukawa, Tōon, Ehime, 791-0295, Japan,
Int J Hematol. 2014 Feb;99(2):123-31. doi: 10.1007/s12185-013-1493-7. Epub 2013 Dec 19.
The functional properties of the adoptive immune response mediated by effector T lymphocytes are decisively regulated by their T-cell receptors (TCRs). Transfer of genes encoding target antigen-specific receptors enables polyclonal T cells to redirect toward cancer cells and virally infected cells expressing those defined antigens. Using this technology, a large population of redirected T cells displaying uniform therapeutic properties has been produced, powerfully advancing their clinical application as "cellular drugs" for adoptive immunotherapy against cancer. Clinically, anticancer adoptive immunotherapy using these genetically engineered T cells has an impressive and proven track record. Notable examples include the dramatic benefit of chimeric antigen receptor gene-modified T cells redirected towards B-cell lineage antigen CD19 in patients with chronic lymphocytic leukemia, and the impressive outcomes in the use of TCR gene-modified T cells redirected towards NY-ESO-1, a representative cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. In this review, we briefly overview the current status of this treatment option in the context of hematological malignancy, and discuss a number of challenges that still pose an obstacle to the full effectiveness of this strategy.
效应T淋巴细胞介导的过继性免疫反应的功能特性由其T细胞受体(TCR)决定性地调控。编码靶向抗原特异性受体的基因转移使多克隆T细胞能够重定向至表达那些特定抗原的癌细胞和病毒感染细胞。利用这项技术,已产生了大量具有一致治疗特性的重定向T细胞,有力地推动了它们作为“细胞药物”在过继性免疫疗法治疗癌症中的临床应用。临床上,使用这些基因工程改造的T细胞进行抗癌过继性免疫疗法有着令人瞩目的且经过验证的记录。显著的例子包括,在慢性淋巴细胞白血病患者中,嵌合抗原受体基因修饰的T细胞重定向至B细胞系抗原CD19带来的显著益处,以及在晚期黑色素瘤和滑膜细胞肉瘤患者中,TCR基因修饰的T细胞重定向至代表性的癌胚抗原NY-ESO-1所取得的令人印象深刻的结果。在本综述中,我们简要概述了这种治疗方案在血液系统恶性肿瘤背景下的现状,并讨论了一些仍然阻碍该策略充分发挥效力的挑战。
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