肿瘤细胞治疗研究
英文原题：Generation and proof-of-concept for allogeneic CD123 CAR-Delta One T (DOT) cells in acute myeloid leukemia.
我们的结果为基于DOT的下一代异体CAR-T疗法治疗AML提供了概念验证。
嵌合抗原受体（CAR）-T细胞已成为复发/难治性血液肿瘤的突破性治疗手段，展现出令人瞩目的完全缓解率。然而，约50%的患者在治疗后1年内复发。T细胞“适应性”对于延长CAR-T的持久性和活性至关重要。来自健康供者的异体T细胞比自体患者来源的T细胞功能失调或耗竭更少；在此背景下，Delta One T细胞（DOTs），一种最近描述的基于MHC/HLA非依赖性V 1 + T细胞的细胞产品，代表了一个有前景的异体平台。
我们首次生成并临床前验证了基于4-1BB的CAR-DOTs，其针对白细胞介素-3链受体（CD123），这是一种在急性髓系白血病（AML）原始细胞上广泛表达的靶抗原。
CD123CAR-DOTs对AML细胞系和原代样本在体外和体内均表现出强烈的细胞毒性，优于对照DOTs，即使在肿瘤再攻击时也是如此。
BACKGROUND: Chimeric antigen receptor (CAR)-T cells have emerged as a breakthrough treatment for relapse/refractory hematological tumors, showing impressive complete remission rates. However, around 50% of the patients relapse before 1-year post-treatment. T-cell 'fitness' is critical to prolong CAR-T persistence and activity. Allogeneic T cells from healthy donors are less dysfunctional or exhausted than autologous patient-derived T cells; in this context, Delta One T cells (DOTs), a recently described cellular product based on MHC/HLA-independent V 1 + T cells, represent a promising allogeneic platform. METHODS: Here we generated and preclinically validated, for the first time, 4-1BB-based CAR-DOTs directed against the interleukin-3 chain receptor (CD123), a target antigen widely expressed on acute myeloid leukemia (AML) blasts. RESULTS: CD123CAR-DOTs showed vigorous, superior to control DOTs, cytotoxicity against AML cell lines and primary samples both in vitro and in vivo , even on tumor rechallenge. CONCLUSIONS: Our results provide the proof-of-concept for a DOT-based next-generation allogeneic CAR-T therapy for AML.
MEMBER ACCOUNT
登录成功会直接打开下一页。
