Feasibility study of a novel preparation strategy for anti-CD7 CAR-T cells with a recombinant anti-CD7 blocking antibody

作者：Ye, Jing; Jia, Yujie; Tuhin, Israth Jahan; Tan, Jingwen; Monty, Masuma Akter; Xu, Nan; Kang, Liqing; Li, Minghao; Lou, Xiaoyan; Zhou, Meixia; Fang, Xiaoyan; Shao, Jiaqi; Zhu, Hongjia; Yan, Zhiqiang^*; Yu, Lei^*

来源：Molecular Therapy-Oncolytics, 2022, 24: 719-728.

DOI：10.1016/j.omto.2022.02.013

• CHIMERIC ANTIGEN RECEPTOR
• MEMORY STEM-CELLS
• B-CELL
• TISAGENLECLEUCEL
• IMMUNOTHERAPY
• MECHANISMS
• EXPRESSION
• LEUKEMIA
• THERAPY
• CD7

Although chimeric antigen receptor (CAR) T cell immunotherapy has shown promising significance in B cell malignancies, success against T cell malignancies remains unsatisfactory because of shared antigenicity between normal and malignant T cells, resulting in fratricide and hindering CAR production for clinical treatment. Here, we report a new strategy of blocking the CD7 antigen on the T cell surface with a recombinant anti-CD7 antibody to obtain a sufficient amount of CD7-targeting CAR-T cells for T cell acute lymphoblastic leukemia (T-ALL) treatment. Feasibility was evaluated systematically, revealing that blocking the CD7 antigen with an antibody effectively blocked CD7-derived fratricide, increased the expansion rate, reduced the proportion of regulatory T (Treg) cells, maintained the stem cell-like characteristics of T cells, and restored the proportion of the CD8(+) T cell population. Ultimately, we obtained anti-CD7 CAR-T cells that were specifically and effectively able to kill CD7 antigen-positive target cells, obviating the need for complex T cell modifications. This approach is safer than previous methods and provides a new, simple, and feasible strategy for clinical immunotherapies targeting CD7-positive malignant tumors.