Dhakal Binod, Chhabra Saurabh, Savani Bipin N, Hamadani Mehdi
Blood & Marrow Transplantation and Cellular Therapy Program, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
Division of Hematology and Oncology, Vanderbilt University, Nashville, TN, USA.
Br J Haematol. 2022 Apr;197(1):28-40. doi: 10.1111/bjh.17904. Epub 2021 Oct 21.
Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy in haematological malignancies. However, the currently approved products are generated from autologous T cells that require orchestration of several logistically complex steps, which include patient eligibility, apheresis capability, complex manufacturing processes and shipping logistics. Use of third-party donor-derived (allogeneic) effector cells that allows the generation of 'off-the-shelf" CAR T cells (allo-CAR) could circumvent many of the problems associated with autologous CAR T-cell therapy. Several allogeneic products are entering clinical trials, and though early, the results look promising. The recognised potential benefits of allo-CAR do not come without significant challenges, that must be overcome for their widespread use. Alloreactivity, i.e. graft-versus-host disease (GVHD), and rejection of donor T cells is one of the major barriers, while other potential barriers include immunogenicity, unknown in vivo persistence, and CAR T-cell yield. In the present review, we provide a comprehensive review of the challenges associated with autologous CAR, the benefits and potential challenges associated with allo-CAR. Finally, we review the available platforms for allo-CAR for B-cell and plasma cell malignancies.
嵌合抗原受体（CAR）T细胞疗法是血液系统恶性肿瘤中一种很有前景的免疫疗法。然而，目前获批的产品是由自体T细胞产生的，这需要精心安排几个后勤复杂的步骤，包括患者资格评估、采血能力、复杂的生产过程和运输物流。使用第三方供体来源（同种异体）的效应细胞来生成“现货”CAR T细胞（异基因CAR，allo-CAR）可以规避许多与自体CAR T细胞疗法相关的问题。几种同种异体产品正在进入临床试验，虽然尚处于早期阶段，但结果看起来很有希望。allo-CAR公认的潜在益处并非没有重大挑战，要使其广泛应用，这些挑战必须克服。同种异体反应性，即移植物抗宿主病（GVHD），以及供体T细胞的排斥是主要障碍之一，而其他潜在障碍包括免疫原性、体内持续时间未知以及CAR T细胞产量。在本综述中，我们全面回顾了与自体CAR相关的挑战、与allo-CAR相关的益处和潜在挑战。最后，我们回顾了用于B细胞和浆细胞恶性肿瘤的allo-CAR可用平台。
