Abstract:
The concept of allogeneic cell therapy was first presented over 60 years ago with hematopoietic stem cell transplantation. However, complications such as graft versus host disease (GVHD) and regimen-related toxicities remained as major obstacles. To maximize the effect of graft versus leukemia, while minimizing the effect of GVHD, donor lymphocyte infusion was utilized. This idea, which was used against viral infections, postulated that adoptive transfer of virus-specific cytotoxic T lymphocytes could reconstitute specific immunity and eliminate virus infected cells and led to the idea of banking third party cytotoxic T cells (CTLs). T cell exhaustion sometimes became a problem and difficulty arose in creating robust CTLs. However, the introduction of induced pluripotent stem cells (iPSCs) lessens such problems, and by using iPSC technology, unlimited numbers of allogeneic rejuvenated CTLs with robust and proliferative cytotoxic activity can be created. Despite this revolutionary concept, several concerns still exist, such as immunorejection by recipient cells and safety issues of gene editing. In this review, we describe approaches to a feasible \"off-the-shelf\" therapy that can be distributed rapidly worldwide. We also offer perspectives on the future of allogeneic cell cancer immunotherapy.
摘要:
异基因细胞治疗的概念在60多年前首次出现在造血干细胞移植中。然而,移植物抗宿主病(GVHD)和治疗方案相关毒性等并发症仍然是主要障碍.为了最大限度地发挥移植物抗白血病的作用,同时最小化GVHD的影响,使用供体淋巴细胞输注。这个想法,用于抵抗病毒感染,假设病毒特异性细胞毒性T淋巴细胞的过继转移可以重建特异性免疫并消除病毒感染的细胞,并导致建立第三方细胞毒性T细胞(CTL)的想法。T细胞耗尽有时会成为一个问题,并且在创建强大的CTL时会出现困难。然而,诱导多能干细胞(iPSCs)的引入减轻了这些问题,通过使用iPSC技术,可以产生无限数量的具有稳健和增殖细胞毒性活性的同种异体再生CTL。尽管有这个革命性的概念,一些担忧仍然存在,例如受体细胞的免疫排斥和基因编辑的安全性问题。在这次审查中,我们描述了一种可行的“现成”疗法的方法,这种疗法可以在全球范围内迅速推广。我们还提供了关于同种异体细胞癌症免疫治疗未来的观点。