Center for Cellular Immunotherapies, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Rutgers New Jersey Medical School, Newark, NJ, USA.
Leuk Lymphoma. 2021 Nov;62(11):2587-2599. doi: 10.1080/10428194.2021.1913146. Epub 2021 Apr 19.
Chimeric antigen receptor (CAR) T cells have emerged as a powerful therapeutic modality for cancer. Following encouraging clinical results, autologous anti-CD19 CAR-T cells first secured regulatory approval from the U.S. Food and Drug Administration in 2017 for the treatment of pediatric B cell acute lymphoblastic leukemia and for diffuse large B cell lymphoma (DLBCL), followed recently by mantle cell lymphoma. While long-term immunosurveillance is among the most important requirements for durable remissions in leukemia and a major potential benefit of immunotherapy, the exact determinants of CAR-T cell persistence remain elusive. Furthermore, it is less clear that long-term persistence is required for durable remission in lymphoma. In this review, we aim to describe the factors governing CAR-T cell persistence as well as unique approaches to exert control over engineered lymphocyte populations post-infusion. Additionally, we explore potential risks and associated clinical considerations arising from prolonged surveillance by highly reactive cytotoxic T lymphocytes.
嵌合抗原受体 (CAR) T 细胞已成为癌症治疗的一种强大手段。在令人鼓舞的临床结果之后，自体抗 CD19 CAR-T 细胞于 2017 年首次获得美国食品和药物管理局的监管批准，用于治疗儿科 B 细胞急性淋巴细胞白血病和弥漫性大 B 细胞淋巴瘤（DLBCL），最近又用于套细胞淋巴瘤。虽然长期免疫监测是白血病持久缓解的最重要要求之一，也是免疫治疗的主要潜在益处之一，但 CAR-T 细胞持续存在的确切决定因素仍难以捉摸。此外，对于淋巴瘤的持久缓解是否需要长期持续存在尚不清楚。在这篇综述中，我们旨在描述控制 CAR-T 细胞持续存在的因素，以及在输注后对工程淋巴细胞群进行控制的独特方法。此外，我们还探讨了由高反应性细胞毒性 T 淋巴细胞进行长期监测所带来的潜在风险和相关临床考虑因素。
