iCell Gene Therapeutics LLC Research & Development Division, Long Island High Technology Incubator, 25 Health Sciences Drive, Stony Brook, NY, 11790, USA.
Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, People's Republic of China.
Stem Cell Rev Rep. 2020 Apr;16(2):369-384. doi: 10.1007/s12015-019-09937-9.
T-cell malignancies often result in poor prognosis and outcome for patients. Immunotherapy has recently emerged as a revolutionary treatment against cancer, and the success seen in CD19 CAR clinical trials may extend to T cell diseases. However, a shared antigen pool coupled with the impact of T-cell depletion incurred by targeting T cell disease remain concepts to be clinically explored with caution. Here we report on the ability of T cells transduced with a CD5CAR to specifically and potently lyse malignant T-cell lines and primary tumors in vitro in addition to significantly improving in vivo control and survival of xenograft models of T-ALL. To extensively explore and investigate the biological properties of a CD5 CAR, we evaluated multiple CD5 CAR constructs and constructed 3 murine models to characterize the properties of CD5 down-regulation, the efficacy and specificity produced by different CD5 CAR construct designs, and the impact of incorporating a CD52 safety switch using CAMPATH to modulate the persistency and function of CAR cells. These data support the potential use of CD5CAR T cells in the treatment of T cell malignancies or refractory disease in clinical settings.
T 细胞恶性肿瘤常导致患者预后不良。免疫疗法最近成为一种对抗癌症的革命性治疗方法，CD19 CAR 临床试验的成功可能扩展到 T 细胞疾病。然而，共同的抗原库加上针对 T 细胞疾病的 T 细胞耗竭的影响仍然是需要谨慎临床探索的概念。在这里，我们报告了转导 CD5CAR 的 T 细胞在体外能够特异性和有效地溶解恶性 T 细胞系和原发性肿瘤，此外还显著改善 T-ALL 异种移植模型的体内控制和存活。为了广泛探索和研究 CD5 CAR 的生物学特性，我们评估了多种 CD5 CAR 构建体，并构建了 3 种小鼠模型来表征 CD5 下调的特性、不同 CD5 CAR 构建体设计产生的疗效和特异性，以及使用 CAMPATH 纳入 CD52 安全开关来调节 CAR 细胞的持久性和功能的影响。这些数据支持在临床环境中使用 CD5CAR T 细胞治疗 T 细胞恶性肿瘤或难治性疾病的潜力。
