Naturally Selected CD7 CAR-T Therapy without Genetic editing Exerts Significant Antitumor Efficacy against Relapsed and Refractory Acute Myeloid Leukemia(R/R-AML)

Abstract

AbstractBackground Survival time for patients with relapsed and refractory acute myeloid leukemia (R/R-AML) remains threatened and treatment appears challenging. Chimeric antigen receptor T cell (CAR-T) has been widely used for hematologic malignancies. Current CAR-T therapies for acute myeloid leukemia mostly target myeloid-lineage antigens such as CD123 and CD33, which may have potential hematopoietic toxicity. CD7, as a lineage-specific receptor, is expressed in acute myeloid leukemia cells and T cells, while not expressed in myeloid cells. Methods In this report, Immunohistochemistry and flow cytometry were used to analyze CD7 expression in clinical samples from R/R-AML patients and healthy donors. we designed naturally selected CD7 CAR-T to analyze various functions and in vitro anti-leukemic efficacy by flow cytometry, while xenograft models were used to validate in vivo tumor dynamics Results we calculated the percentage of CD7 expression in our institution's AML patients with minimal residual disease (MRD) (5/16, 31.25%) and tested CD7 in myeloid and lymphoid lineage cells of R/R-AML patients, concluding that CD7 is expressed in T cells and not in myeloid cells, similar to previous studies. Subsequently, we constructed and designed a naturally selected CD7 CAR-T (CD7 CAR). We did not perform CD7 antigen knockdown on CD7 CAR-T cells, but it naturally eliminated CD7 molecule expression at the end of the culture cycle and then evaluated its ability to target and kill the acute myeloid leukemia cell line MOLM-13 in vitro and in vivo. CD7 CAR-T cells efficiently murder acute myeloid leukemia cells in vitro and significantly inhibit the growth of leukemia cells in xenograft model mice. Conclusion Naturally Selected CD7 CAR-T cells were proven to be an effective and safe treatment strategy for relapsed refractory acute myeloid leukemia in preclinical studies.