Ye Xueshuai, Ge Min, Tan Mengtian, Wu Yongqiang, Zhang Haiqiang, Fu Zexian
Affiliated Hospital of Hebei Engineering University and School of Clinical Medicine, Hebei University of Engineering, Handan, China.
Gene Editing Research Center, Hebei University of Science and Technology, Shijiazhuang, China.
Front Immunol. 2025 Mar 4;16:1490491. doi: 10.3389/fimmu.2025.1490491. eCollection 2025.
CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has achieved marvelous results in the treatment of patients with relapsed and/or refractory B-cell lymphomas, B-cell acute lymphoblastic leukemia, and multiple myeloma. As a new treatment method that has changed the existing treatment paradigm, there has been a short time from its emergence to FDA approval. However, with the increasing number of cases and the passage of time, hidden problems have gradually been exposed. In this review, we summarize the short- and long-term toxicity, such as secondary T-cell tumors and lethal CAR tumors, of patients with hematologic malignancies treated with CD19-CAR-T cells, including cytokine release syndrome (CRS), ICANS, and secondary malignancies with low occurrence rates but high mortality, such as secondary T cell tumors and lethal CAR tumors, which may be related to the gene modification mechanism of viral vectors currently approved for CAR-T cells. We also discuss potential investigational strategies designed to improve the safety of CAR-T-cell therapy.
靶向CD19的嵌合抗原受体（CAR）T细胞疗法在治疗复发和/或难治性B细胞淋巴瘤、B细胞急性淋巴细胞白血病和多发性骨髓瘤患者方面取得了显著成效。作为一种改变了现有治疗模式的新治疗方法，从其出现到获得美国食品药品监督管理局（FDA）批准的时间很短。然而，随着病例数量的增加和时间的推移，一些潜在问题逐渐暴露出来。在这篇综述中，我们总结了接受CD19-CAR-T细胞治疗的血液系统恶性肿瘤患者的短期和长期毒性，如细胞因子释放综合征（CRS）、免疫效应细胞相关神经毒性综合征（ICANS），以及发生率低但死亡率高的继发性恶性肿瘤，如继发性T细胞肿瘤和致死性CAR肿瘤，这些可能与目前已获批准用于CAR-T细胞的病毒载体的基因修饰机制有关。我们还讨论了旨在提高CAR-T细胞疗法安全性的潜在研究策略。
