TCR基因免疫治疗中优化转TCR基因配对的研究进展

TCR基因修饰T细胞的过继性免疫治疗是指将识别肿瘤抗原的特异性TCR基因转导至外周血T细胞,经大量扩增后回输给患者,从而发挥抗肿瘤效应的一种治疗技术。目前TCR基因治疗所面临的关键问题之一是如何改造修饰转TCR基因使得转TCR α链和β链在T细胞表面优先配对以提高转T细胞的功能,并避免off-target反应毒性的产生。最近,各种基因修饰策略被用于优化转TCR基因配对和减少错配。介绍了近年来针对TCR基因进行修饰改造的各种策略及TCR基因治疗的临床试验。

Advances in Research on Optimization of Transgenic TCR Pairing in TCR Gene Therapy

TCR genes adoptive therapy is a clinical promise approach for the treatment of cancer. Using ex vivo gene transfer, T cells isolated from patients can be genetically engineered to express a novel TCR, and then the engineered T cells re-infuse back into the patient to specifically recognize a tumor-associated antigen and thereby selectively kill tumor cells. One of the current challenges of TCR gene therapy is the optimization of TCR α and β transgene pairing to enhance the functional avidity of therapeutic T cells and avoid the off-target toxicity. Recently, various genetically modified TCRs have been developed that enhance TCR pairing and minimize mispairing. The strategies of optimization the transgenic TCR pairing and the clinical trials with TCR gene therapy were summarized.