Jambon Samy, Sun Jianping, Barman Shawn, Muthugounder Sakunthala, Bito Xue Rachel, Shadfar Armita, Kovach Alexandra E, Wood Brent L, Thoppey Manoharan Varsha, Morrissy A Sorana, Bhojwani Deepa, Wayne Alan S, Pulsipher Michael A, Kim Yong-Mi, Asgharzadeh Shahab, Parekh Chintan, Moghimi Babak
Division of Hematology and Oncology, Department of Pediatrics, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.
Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, California.
Blood Cancer Discov. 2025 Jan 8;6(1):55-72. doi: 10.1158/2643-3230.BCD-23-0258.
Our study demonstrates the use of "IF-THEN" SynNotch-gated CAR-T cells targeting CD33 and CD123 in AML reduces off-tumor toxicity. This strategy enhances T-cell phenotype, improves expansion, preserves HSPCs, and mitigates cytokine release syndrome-addressing critical limitations of existing AML CAR-T therapies.
我们的研究表明，在急性髓系白血病（AML）中使用靶向CD33和CD123的“如果-那么”（IF-THEN）合成Notch受体门控嵌合抗原受体（CAR）T细胞可降低肿瘤外毒性。该策略增强了T细胞表型，改善了细胞扩增，保护了造血干细胞，并减轻了细胞因子释放综合征，解决了现有AML CAR-T疗法的关键局限性。
