[Killing Effect of A CD7 Chimeric Antigen Receptor-Modified NK-92MI Cell Line on CD7-Positive Hematological Malignant Cells]

Abstract

Objective: To investigate the killing effect of NK-92MI cells modified by chimeric antigen receptor (CD7-CAR) and specifically targeting CD7 to CD7⁺ hematological malignant cells.

Methods: Three types of hematological malignant tumor cells, including 5 cases of CD7⁺ acute T-lymphoblastic leukemia (T-ALL), 10 cases of acute myeloid leukemia (AML) and 6 cases of T-cell lymphoma were collected, centrifuged, cultured and used to detect the expression levels of tumor cell surface targets; 7-AAD, CD56-APC, CD3-FITC, IgG Fc-PE flow cytometry were used to detected the transfection efficiency of NK-92MI and CD7-CAR-NK-92MI cells, killing efficiencies of CD7-CAR-NK-92MI cells to CD7⁺ hematological tumor cells in vitro were determined by flow cytometry using PE Annexin V Apoptosis Detection Kit. Secretion differences of NK-92MI and CD7-CAR-NK-92MI cytokines interleukin (IL)-2, interferon (IFN)-γ, and granzyme B detection were estimated by using CBA kit.

Results: The killing efficiencies of CD7-CAR-modified NK-92MI cells to CD7⁺ T-ALL, AML, T-cell lymphoma tumor cells were significantly higher than those of NK-92MI cells without genetical modification. The difference showed statistically significant (P＜0.05). The level of IFN-γ and granzyme B were significantly increased among cytokines secreted by CD7-CAR-modified NK-92MI cells as compared with those of NK-92MI cells without genetical modification (P＜0.05) .

Conclusion: CD7-CAR-modified NK-92MI cells have significantly improved killing efficiency against CD7⁺ T-ALL, AML and T lymphoma cells, and shows specific targeting effects, which provides a clinical basis for the treatment of CD7⁺ hematological malignancies.