Journal
MOLECULAR THERAPY-ONCOLYTICS
Volume 24, Issue -, Pages 719-728Publisher
CELL PRESS
DOI: 10.1016/j.omto.2022.02.013
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Funding
- National Natural Science Foundation of China [81872812, 82073800]
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This article reports a new strategy of blocking the CD7 antigen on T cells using a recombinant anti-CD7 antibody to obtain sufficient CD7-targeting CAR-T cells for the treatment of T cell acute lymphoblastic leukemia (T-ALL). The feasibility of this approach was systematically evaluated, showing that blocking the CD7 antigen effectively prevented fratricide, increased expansion rate, reduced the proportion of regulatory T cells, maintained the stem cell-like characteristics of T cells, and restored the proportion of CD8(+) T cells.
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.
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