异基因嵌合抗原受体疗法在浆细胞和淋巴系统恶性肿瘤中的前景与风险
Promise and pitfalls of allogeneic chimeric antigen receptor therapy in plasma cell and lymphoid malignancies.
作者信息
Dhakal Binod, Chhabra Saurabh, Savani Bipin N, Hamadani Mehdi
机构信息
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.
出版信息
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。