First Center Clinical College, Tianjin Medical University, Tianjin, 300192, China.
Department of Hematology, Tianjin First Central Hospital, Tianjin, 300192, China.
Curr Treat Options Oncol. 2023 May;24(5):409-441. doi: 10.1007/s11864-023-01061-8. Epub 2023 Apr 3.
Chimeric antigen receptor (CAR) cell therapy offers patients with hematological malignancies a new therapeutic option. Traditionally, autologous T cells are used to generate CAR designed T cells for each patient. However, this method has several drawbacks, the development of allogeneic CAR cell therapy would be a promising breakthrough that could address several of these limitations. From the clinical trials that have published data, the efficacy of allogeneic CAR cell therapy did not meet the expectations. Because of the host-versus-graft (HvG) effect, allogeneic CAR cells are eliminated by the host, resulting in short-term persistence of allogeneic CAR cells and poor efficacy. It is critical to solve the HvG effect of allogeneic CAR cells. The current commonly used methods are suppressing the host's immune system, using HLA-matched homozygous donors, reducing the expression of HLA, targeting alloreactive lymphocytes and eliminating anti-CAR activities. In this review, we will focus on the HvG effect of the "off-the-shelf" allogeneic CAR cell therapy, especially its mechanism and current methods to solve this problem and summarize relevant clinical trial data.
嵌合抗原受体 (CAR) 细胞疗法为血液系统恶性肿瘤患者提供了一种新的治疗选择。传统上，使用自体 T 细胞为每位患者生成设计的 CAR 靶向 T 细胞。然而，这种方法有几个缺点，同种异体 CAR 细胞疗法的发展将是一个有前途的突破，可以解决其中的一些限制。从已经发表数据的临床试验来看，同种异体 CAR 细胞疗法的疗效并未达到预期。由于宿主抗移植物 (HvG) 效应，同种异体 CAR 细胞被宿主消除，导致同种异体 CAR 细胞的短期持续存在和疗效不佳。解决同种异体 CAR 细胞的 HvG 效应至关重要。目前常用的方法是抑制宿主的免疫系统、使用 HLA 匹配的纯合供体、降低 HLA 的表达、靶向同种反应性淋巴细胞和消除抗 CAR 活性。在这篇综述中，我们将重点关注“现成”同种异体 CAR 细胞疗法的 HvG 效应，特别是其机制和目前解决这一问题的方法，并总结相关的临床试验数据。
