CD147-specific chimeric antigen receptor T cells effectively inhibit T cell acute lymphoblastic leukemia.

Abstract

T cell acute lymphoblastic leukemia (T-ALL) is invasive and heterogeneous, and existing therapies are sometimes unsuccessful. Chimeric antigen receptor (CAR) T cell therapy is a breakthrough tumor treatment method, particularly for B cell acute lymphoblastic leukemia. We found that CD147 was highly expressed in tumor T cells of T-ALL patients and T cell lymphoma. Therefore, CD147-CAR T cells that contain a humanized single-chain variable fragment targeting human CD147 and a second-generation CAR frame were constructed for treating T-ALL. CD147-CAR T cells were able to maintain a healthy proliferation rate, preserving a subset of CD62L+/CCR7+ memory T cells. CD147-CAR T cells showed a potent anti-tumor activity against human T-ALL cell line and T-ALL blasts, releasing high level of cytokines in the process. However, CD147-CAR T cells exhibited potential safety toward human normal cells and CD147-deficent cells. NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt mice were used to establish a T-ALL xenograft model and CD147-CAR T cells conferred robust protection against T-ALL progression and significantly improved survival in mice. Overall, we found that CD147 is a potential antigen target of CAR T cell therapy for T-ALL.

• Authors: Nai-Shan Zheng, Xiang-Yu Zhao, Ding Wei, Jin-Lin Miao, Ze-Kun Liu, Yu-Le Yong, Ren-Yu Zhang, Yi-Xiao Guo, Lin He, Bin Wang, Xiu-Xuan Sun, Hai-Jiao Yang, Tian-Jiao Zhang, Qian He, Xiao-Min Li, Hai Zhang, Rong Hou, Peng Lin, Ying-Ming Xu, Xiao-Jun Huang, Zhi-Nan Chen, Huijie Bian
• Journal: Cancer letters (Cancer Lett) Vol. 542 Pg. 215762 (08 28 2022) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 35659513 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• BSG protein, human
• Receptors, Antigen, T-Cell
• Receptors, Chimeric Antigen
• Basigin

Topics

• Animals
• Basigin (immunology)
• Cell Line, Tumor
• Humans
• Immunotherapy, Adoptive (methods)
• Mice
• Mice, Inbred NOD
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (therapy)
• Receptors, Antigen, T-Cell (immunology)
• Receptors, Chimeric Antigen (immunology)
• T-Lymphocytes