Primary CD33-targeting CAR-NK cells for the treatment of acute myeloid leukemia

Clinical application of CD33-CAR-T cells remains challenging due to potential side effects and its restriction to autologous products. We report on the generation of primary CD33-CAR-NK cells, which are highly effective in combating AML in vitro and in AML xenograft models. Transgene integration by BaEV-LV resulted in 35-60% CAR-expression and CD33-CAR-NK cells displayed unimpeded ex vivo-expansion as well as increased cytotoxicity against CD33+ OCI-AML2 cells compared to untransduced (UTD)-NK cells in vitro. Using an OCI-AML2 NSG-SGM3 xenograft mouse model (n=7/group) a significant reduction of leukemic burden by day 21 could be observed following weekly injections (three in total) of 10e7 CAR-NK cells i.v. BLI-analysis of femur, tibia and spleen on day 22 revealed impeded AML engraftment in CAR-NK cell-treated mice which was confirmed by flow cytometry analysis of isolated BM and spleen. Furthermore, NK cell infiltration in the BM and spleen was significantly increased in mice which received CAR-NK cells and the majority were identified as CAR+ (>73%). Chimerism analysis of peripheral blood revealed higher persistence of NK cells and absence of AML cells in CAR-NK-treated mice.

Publication History

Article published online:
17 May 2022