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

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

Molecular Therapy: Oncolytics (Mar 2022)

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

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

Affiliations

Jing Ye: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
Yujie Jia: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
Israth Jahan Tuhin: Shanghai Unicar Therapy Bio Medicine Technology Co. Ltd., Shanghai 201612, P.R. China
Jingwen Tan: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
Masuma Akter Monty: Shanghai Unicar Therapy Bio Medicine Technology Co. Ltd., Shanghai 201612, P.R. China
Nan Xu: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
Liqing Kang: Shanghai Unicar Therapy Bio Medicine Technology Co. Ltd., Shanghai 201612, P.R. China
Minghao Li: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
Xiaoyan Lou: Shanghai Unicar Therapy Bio Medicine Technology Co. Ltd., Shanghai 201612, P.R. China
Meixia Zhou: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
Xiaoyan Fang: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
Jiaqi Shao: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
Hongjia Zhu: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China
Zhiqiang Yan: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China; Corresponding author Lei Yu, Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China.
Lei Yu: Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China; Corresponding author Zhiqiang Yan, Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, P.R. China.

Journal volume & issue: Vol. 24
pp. 719 – 728

Abstract

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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.

Published in Molecular Therapy: Oncolytics

ISSN: 2372-7705 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: http://www.cell.com/molecular-therapy-family/oncolytics/latest-content

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