CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:"Off-the-Shelf" Allogeneic CAR Cell Therapy-Neglected HvG Effect.
"Off-the-Shelf" Allogeneic CAR Cell Therapy-Neglected HvG Effect.
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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CAR设计的T细胞。然而,这种方法存在若干缺点,异体CAR细胞疗法的发展将是一个有前景的突破,可以解决其中的一些局限性。从已发表数据的临床试验来看,异体CAR细胞疗法的疗效未达到预期。由于宿主抗移植物(HvG)效应,异体CAR细胞被宿主清除,导致异体CAR细胞持久性短和疗效差。解决异体CAR细胞的HvG效应至关重要。目前常用的方法包括抑制宿主免疫系统、使用HLA匹配的纯合供者、降低HLA表达、靶向同种反应性淋巴细胞以及消除抗CAR活性。在这篇综述中,我们将聚焦于“现货型”异体CAR细胞疗法的HvG效应,特别是其机制和当前解决该问题的方法,并总结相关临床试验数据。
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.
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