A Clinical Study On Cd33-Directed Chimeric Antigen Receptormodified Nkcells In Patient With Refractory Or Relapsed Acute Myeloid Leukemia

In patients with acute myeloid leukemia, an about 20-40% of the patients show no response to current therapy, and about 50-70% of the patients relapse after complete response (CR). These patients represent the majority of the refractory or relapsed acute myeloid leukemia (R/R AML). The 1-year survival rate of those patients is limited to 9 allogeneic CD33-CAR-NK cells were infused. Approximately 10% of the infused cells were confirmed to be transduced with the CAR. The protocol was to infuse 1 x 10 9 CD33-CAR-NK cells and repeated every other day for three times. After CD33-CAR-NK cell infusion, the main side effects include repeated low-grade fever and significant rises of serum cytokines, e.g. IFN-γ, TNF-α, IL-2, IL-6 and IL-10. However, before discharge, the level of the cytokines reduced to normal. In addition, while we detected K + , Ca 2+ , creatinine and glutamic-pyruvic transaminase after CAR-NK infusion, all of these were not significantly changed compared with those before the CAR-NK infusion. These results suggested that there was no significant tumor necrosis after treatment. After CD33-CAR-NK cell infusions, the proportion of leukemic cells in the patient9s bone marrow decreased significantly. For example, in one of the two AML-M1 patients, a 53 year-old male, the proportion of leukemic cells in bone marrow reduced from 40% to 26% after CD33-CAR-NK cell infusion. In addition, the proportion of the CD33 + cells in bone marrow reduced from 48.82% to 32.56%, and the CD33 + CD34 + cells in bone marrow reduced from 40.59% to 27.26% respectively. This initial clinical work indicates that CD33-CAR-NK therapy may offer a new therapeutic option for R/R AML, which aims to reduce the tumor burden, eliminate LSCs, and provide an opportunity to combine its use with other therapies for more effective treatment of the R/R AML patients. Key words : Refractory or relapsed acute myeloid leukemia (R/R AML), CD33, Chimeric antigen receptor (CAR), NK cells, Immunotherapy. Citation Format: Leiming Xia, Xiang Sun, Liu Liu, Yi Wang, Tan Li, Bin Li, Gregory Wolf, Qiao Li, Lin Yang, Yangyi Bao. A clinical study on CD33-directed chimeric antigen receptormodified NKcells in patient with refractory or relapsed acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT060.