肿瘤细胞治疗研究
英文原题：The race between 4-1BB- and CD28-based CD19 CAR-T products in the therapy of B-cell malignancies.
靶向 CD19 的CAR-T 细胞疗法彻底改变了 B 细胞恶性肿瘤的治疗。
靶向 CD19 的CAR-T 细胞疗法已经彻底改变了 B 细胞恶性肿瘤的治疗。影响 CAR-T 疗效和持久性的关键因素之一是共刺激结构域，其中 4-1BB 和 CD28 成为两种主要信号平台。虽然基于 CD28 的 CAR-T 细胞表现出强大的初始效力和快速扩增，但基于 4-1BB 的 CAR-T 细胞显示出更强的持久性和长期疗效。然而，对 CAR-T 疗法的耐药性仍然是一个重大挑战。肿瘤细胞发展出多种机制来逃避免疫监视，包括由表观遗传因素或 CD19 基因遗传异常导致的 CD19 抗原逃逸。这篇综述文章总结了两种共刺激结构域之间的机制差异、它们对临床结局的影响，以及它们可能如何影响耐药性的发生。通过剖析效力之战和持久性竞赛，我们为 B 细胞恶性肿瘤 CAR-T 疗法不断演变的格局提供了见解。
Chimeric antigen receptor T-cell (CAR-T) therapy targeting CD19 has revolutionized the treatment of B-cell malignancies. One of the critical factors influencing CAR-T efficacy and durability is the costimulatory domain, with 4-1BB and CD28 emerging as the two dominant signaling platforms. While CD28-based CAR-T cells exhibit strong initial potency and rapid expansion, 4-1BB-based CAR-T cells demonstrate greater persistence and long-term efficacy. However, resistance to CAR-T therapy remains a significant challenge. Tumor cells develop a variety of mechanisms to evade immune surveillance, including CD19 antigen escape due to epigenetic factors or genetic aberrations of the CD19 gene. This review article summarizes the mechanistic differences between both costimulatory domains, their impact on clinical outcomes, and how they might influence resistance occurrence. By dissecting the battle of potency and the race of persistence, we provide insights into the evolving landscape of CAR-T therapy for B-cell malignancies.
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