Abstract CT060: A clinical study on CD33-directed chimeric antigen receptormodified NKcells in patient with refractory or relapsed acute myeloid leukemia
Authors: Xia Leiming , Sun Xiang , Liu Liu , Wang Yi , Li Tan , Li Bin , Wolf Gregory , Li Qiao , Yang Lin , Bao Yangyi 
Published: August 2018

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 &lt;30% and it further drops to approximately 10% for 5-year survival. More effective treatment for this disease is urgently needed. As a new type of cell-based immune therapy, chimeric antigen receptor modified NK (CAR-NK) cell treatment is now promising in treating hematological malignancies. CD33 is found to be expressed at higher levels on both AML cells and leukemia stem cells (LSCs) compared with normal hematopoietic stem cells (HPSCs). Therefore, use of CD33-directed chimeric antigen receptor modified NK cells (CD33-CAR-NK) may lead to the development of a novel method for the treatment of R/R AML patients. In this study, three patients with R/R AML expressing high level of CD33 (40-70%) were enrolled in a clinical study; two were M1, and one was M2a. All three patients had received a series of standard treatments with no therapeutic effect before 3 x 109 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 109 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+, Ca2+, 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 patient's 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.