Division of General Internal Medicine, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Eur J Haematol. 2024 Feb;112(2):197-210. doi: 10.1111/ejh.14074. Epub 2023 Aug 6.
The success of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies has realized a longstanding effort toward harnessing the immune system to fight cancer in a truly personalized fashion. Second generation chimeric antigen receptors (CAR) incorporating co-stimulatory molecules like 4-1BB or CD28 were able to overcome some of the hindrances with initial CAR constructs resulting in efficacious products. Many second-generation CAR-T products have been approved in the treatment of relapsed/refractory hematologic malignancies including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and acute lymphoblastic leukemia. However, challenges remain in optimizing the manufacturing, timely access, limiting the toxicity from CAR-T infusions and improving sustainability of responses derived with CAR-T therapy. Here, we summarize the clinical trial data leading to approval CAR-T therapies in MM and NHL, discuss the limitations with current CAR-T therapy strategies and review emerging strategies for overcoming these limitations.
嵌合抗原受体 T 细胞（CAR-T）疗法在血液恶性肿瘤中的成功实现了长期以来以真正个性化的方式利用免疫系统对抗癌症的努力。包含共刺激分子如 4-1BB 或 CD28 的第二代嵌合抗原受体（CAR）能够克服初始 CAR 构建体的一些障碍，从而产生有效的产品。许多第二代 CAR-T 产品已被批准用于治疗复发/难治性血液恶性肿瘤，包括多发性骨髓瘤（MM）、非霍奇金淋巴瘤（NHL）和急性淋巴细胞白血病。然而，在优化制造、及时获得、限制 CAR-T 输注的毒性以及提高 CAR-T 治疗获得的反应可持续性方面仍然存在挑战。在这里，我们总结了导致 MM 和 NHL 中 CAR-T 疗法批准的临床试验数据，讨论了当前 CAR-T 治疗策略的局限性，并回顾了克服这些局限性的新策略。
