现成的(OTS)过继性T细胞疗法具有许多好处,例如立即可用,改善访问和降低成本,但是面对移植物抗宿主病(GVHD)和移植物排斥的主要挑战,由移植物和宿主中存在的同种反应性T细胞介导,分别。我们通过使用表达靶向CD30的嵌合抗原受体(CAR)的爱泼斯坦-巴尔病毒(EBV)特异性T细胞(EBVST)开发了OTST细胞治疗平台。同种异体EBVST在几项临床试验中没有引起GVHD,而CD30。汽车,对淋巴瘤的治疗有效,还可以靶向在激活时上调CD30的同种异体反应性T细胞。尽管EBVST表达高水平的CD30,但它们在顺式中受到保护,CD30汽车。因此,它们可以通过其天然EBV特异性T细胞受体和CD30广泛增殖并维持功能。汽车。CD30CAR使EBVST能够与幼稚和引发的同种异体反应性T细胞在共培养中持续存在,并消除也可能具有同种反应性的活化自然杀伤细胞。总之,我们显示CD30。CAREBVST有潜力成为一种有效的OTS治疗CD30+肿瘤,如果成功,然后可以用作靶向其他肿瘤抗原的平台。
Off-the-shelf (OTS) adoptive T cell therapies have many benefits such as immediate availability, improved access and reduced cost, but face the major challenges of graft-vs-host disease (GVHD) and graft rejection, mediated by alloreactive T cells present in the graft and host, respectively. We have developed a platform for OTS T cell therapies by using Epstein-Bar virus (EBV)-specific T cells (EBVSTs) expressing a chimeric antigen receptor (CAR) targeting CD30. Allogeneic EBVSTs have not caused GVHD in several clinical trials, while the CD30.CAR, that is effective for the treatment of lymphoma, can also target alloreactive T cells that upregulate CD30 on activation. Although EBVSTs express high levels of CD30, they were protected from fratricide in cis, by the CD30.CAR. Hence, they could proliferate extensively and maintained function both through their native EBV-specific T cell receptor and the CD30.CAR. The CD30.CAR enabled EBVSTs to persist in co-cultures with naive and primed alloreactive T cells and eliminate activated natural killer cells that can also be alloreactive. In conclusion, we show that CD30.CAR EBVSTs have the potential to be an effective OTS therapy against CD30+ tumors and, if successful, could then be used as a platform to target other tumor antigens.