Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, Rui Jin Hospital, National Research Center for Translational Medicine at Shanghai, Shanghai Jiao Tong University School of Medicine, 200000, Shanghai, China.
Department of Neurology, Zhongshan Hospital, Fudan University, 200000, Shanghai, China.
Invest New Drugs. 2023 Apr;41(2):220-225. doi: 10.1007/s10637-023-01344-9. Epub 2023 Mar 29.
Chimeric antigen receptor T (CAR-T) cell therapy has become a research hotspot in the field of hematological malignancies. However, CAR-T cell therapy can lead to immunotherapy-associated side effects including cytokine release syndrome and neurotoxicity. Gene depletion of GM-CSF in CAR-T cells was found preventive against adverse effects, but additional transfections were required to produce CAR-T cells. In this study, we interrupted GM-CSF expression in CAR-T cells by inserting the GM-CSF shRNA-expression cassette in the CAR vector. Reduction of GM-CSF in CAR-T cells could decrease the level of several proinflammatory cytokines without hampering the killing capacity. The manufacture of GM-CSF knockdown CAR-T cells does not require complicated transfections, which makes it more practical and feasible for clinical application.
嵌合抗原受体 T (CAR-T) 细胞疗法已成为血液系统恶性肿瘤领域的研究热点。然而，CAR-T 细胞疗法可导致免疫治疗相关的副作用，包括细胞因子释放综合征和神经毒性。在 CAR-T 细胞中基因敲除 GM-CSF 被发现可预防不良反应，但需要额外的转染来产生 CAR-T 细胞。在这项研究中，我们通过在 CAR 载体中插入 GM-CSF shRNA 表达盒来中断 CAR-T 细胞中的 GM-CSF 表达。CAR-T 细胞中 GM-CSF 的减少可以降低几种促炎细胞因子的水平，而不影响杀伤能力。GM-CSF 敲低 CAR-T 细胞的制造不需要复杂的转染，使其更实用和更适合临床应用。
