Hematopoietic lineage-converted T cells carrying tumor-associated antigen-recognizing TCRs effectively kill tumor cells

• Main Authors: Fangxiao Hu, Dehao Huang, Yuxuan Luo, Peiqing Zhou, Cui Lv, Kaitao Wang, Qitong Weng, Yuxian Guan, Jiekai Chen, Jinyong Wang, Hongling Wu
• Format: Article
• Language: English
• Published: BMJ Publishing Group 2020-07-01
• Series: Journal for ImmunoTherapy of Cancer
• Online Access: https://jitc.bmj.com/content/8/2/e000498.full

Tumor-associated antigen (TAA) T-cell receptor (TCR) gene-engineered T cells exhibit great potential in antitumor immunotherapy. Considering the high costs and low availability of patient-derived peripheral blood T cells, substantial efforts have been made to explore alternatives to natural T cells. We previously reported that enforced expression of Hoxb5 converted B cells into induced T (iT) cells in vivo. Here, we successfully regenerated naive OT1 (major histocompatibility complex I restricted ovalbumin antigen) iT cells (OT1-iT) in vivo by expressing Hoxb5 in pro-pre-B cells in the OT1 transgenic mouse. The OT1-iT cells can be activated and expanded in vitro in the presence of tumor cells. Particularly, these regenerated OT1-iT cells effectively eradicated tumor cells expressing the TAA (ovalbumin) both in vitro and in vivo. This study provides insights into the translational applications of blood lineage-transdifferentiated T cells in immunotherapy.