Baoqiang Kang, Shuoting Wang, Xinrui Guo, Huaisong Lin, Han Yan, Mingquan Wang, Tianhe Song, Zhishuai Zhang, Xing Hu, Yanling Zhu, Bo Feng, Jinfu Nie, Jiajun Liu, Guangjin Pan
Generation of CAR macrophages from induced pluripotent stem cells(iPSCs) hold great potential for immunotherapy, particularly against T-cell malignancies which are challenging in CAR-T therapy.However, the tumoricidal activity of human iPSCs derived CAR-macrophages (iCAR-Ms) remains less extensively analyzed.Here, we generated human iCAR-Ms targeting CD5 for T-cell malignancy therapy.iCAR-Ms show up-regulation of immunity related functions as well as tumoricidal activity against different T malignant cells expressing CD5.However, the tumoricidal activity of iCAR-Ms is highly related to CD5 density on tumor cells and depends on high dose treatment in vivo.We further reveal that the tumor cells resisting iCAR-M killing show reversible CD5 loss mediated by iCAR-M trogocytosis.In contrast, the retrieved iCAR-Ms from tumor cell co-culture retained tumoricidal activity on new tumor cell expressing CD5.Thus, we identify trogocytosis as an important limiting factor on iCAR-Ms therapy, providing a rationale for developing enhanced CAR-M therapies.