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B.A. Williams et al.
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Figure 7. iCD16+NK-92 +/- 7G3 or isotype control treatment of primary acute myeloid leukemia (AML) xenografted mice. NOD/SCID gammanull (NSG) mice were inoculated intravenously (i.v.) with 3x106 passage human AML spleen-derived cells (day 0) and treated with iCD16+NK-92 +/- 7G3 or BM4 x 5 doses [intraperitoneal injection (i.p.)] (3x/week) starting on day 3 (A). Controls included no therapy and antibodies alone (n=5 for all groups). Survival was determined using Kaplan-Meier survival analysis with a log rank test (B).
model, which can be enhanced using CD16+NK-92 com- bined with an anti-CD123 monoclonal antibody. This provides the first proof-of-principle for the targeting of LSCs by combining an antibody and a standardized cellu- lar therapy. A humanized version of 7G3 (CLS362) is being tested in clinical trials for AML, but is reliant upon a patient’s endogenous NK-cell function for efficacy. Combination therapy with ADCC capable NK cell lines such as CD16+NK-92 or the new haNK platform (CD16+IL-2+NK-92) with CSL362 would enable the thera- peutic translation of our approach into a clinical trial in the future. haNK cells are currently in clinical trials for solid tumors in combination with FDA-approved monoclonal antibodies. The approach we have demonstrated can be readily applied to enhance the targeting of any antigen,
and its particular novelty here is in demonstrating the tar- geting of a cancer stem cell marker and a consequent improvement in survival in a murine AML xenograft model.
Funding
BW was supported by a Terry Fox Foundation Award from the National Cancer Institute of Canada, CIHR clinician scientist training award, as well as grants from the Hospital for Sick Children, Ontario Cancer Institute and University of Toronto. AK was supported by the Gloria and Seymour Epstein Chair in Cell Therapy and Transplantation at the University Health Network and University of Toronto. We would like to acknowl- edge the generous provision of 7G3 for some experiments by Angel Lopez.
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haematologica | 2018; 103(10)