Killing Effect Of A CD7 Chimeric Antigen Receptor-Modified NK-92MI Cell Line On CD7-positive Hematological Malignant Cells

Objective:In recent years,adoptive cellular immunotherapy has developed rapidly, gradually becoming a powerful force against cancer,and is expected to play a good role in treating patients with relapsed and refractory tumors.The method of re-editing the CAR-T cells obtained from the patient's autologous T lymphocytes by using the chimeric antigen receptor(CAR)to target the patient's malignant tumor cells has achieved remarkable results.At present,CAR cell therapy based on T lymphocytes and NK cells has been successfully conducted in clinical phase I/II trials in hematological malignancies,including acute lymphocytic leukemia(ALL),malignant lymphoma,and chronic lymphocytic leukemia.(CLL)and so on.CAR-T cells targeting CD19 successfully induced long-term remission in patients with acute B lymphocytic leukemia.Currently,many clinical trials of CAR-T cells and experimental research on different antigen targets are in the preclinical development stage.In contrast to the large number of pre-clinical and clinical trials of CAR-T cells,currently little is known about the research and efficacy of CAR-engineered NK cells for the treatment of malignant tumors,and most experimental studies are still in the preclinical stage.This study investigated the killing effect of NK-92MI cells modified by chimeric antigen receptor(CD7-CAR)specifically targeting CD7 molecules on CD7~+hematological malignancies.Methods:Based on clinical diagnosis and laboratory flow cytometry results,5 cases of CD7~+acute T-lymphoblastic leukemia(T-ALL)and 10 cases of acute myeloid leukemia(AML)were collected.And 6 cases of T cell lymphoma type 3 hematological malignant tumor cells,centrifuged in the laboratory,cultured to detect the expression level of tumor cell surface targets;NK-92MI and CD7-CAR-NK-92MI cells were detected by flow cytometry The transfection efficiency of CD7-CAR-NK-92MI cells was measured by 7-AAD and Ig G Fc-PE on CD7~+blood tumor cells in vitro.CBA kit was used to detect the secretion of NK-92MI and CD7-CAR-NK-92MI cytokines interleukin(IL)-2,interferon(IFN)-?and granzyme B after killing.Results:The killing efficiency of CD7-CAR-modified NK-92MI cells against CD7~+T-ALL,AML,T-cell lymphoma tumor cells was significantly higher than that of NK-92MI cells that were not genetically modified.The difference was statistically significant(P<0.05).The level of IFN-?was significantly increased in cytokines secreted by CD7-CAR-modified NK-92MI cells compared with NK-92MI cells not genetically modified(P<0.05).Conclusion:CD7-CAR-modified NK-92MI cells have significantly improved killing efficiency against CD7-positive T-ALL,AML and T lymphoma cells,and have specific targeting effects,which provides a clinical basis for the treatment of CD7~+ hematological malignancies.