Purpose: Older acute myeloid leukemia (AML) patients have a poor prognosis, therefore novel therapies are needed. Allogeneic natural killer (NK) cells have been adoptively transferred with promising clinical results. Here, we report the first-in-human study exploiting an unique scalable NK cell product generated ex vivo from CD34+ hematopoietic stem and progenitor cells (HSPCs) from partially HLA-matched umbilical cord blood units. Experimental Design: Ten older AML patients in morphologic complete remission received an escalating HSPC-NK cell dose (between 3 and 30x10^6/kg body weight) after lymphodepleting chemotherapy without cytokine boosting. Results: HSPC-NK cell products contained a median of 75% highly activated NK cells, with <1x10^4 T cells/kg and <3x10^5 B cells/kg body weight. HSPC-NK cells were well tolerated and no graft-versus-host disease nor toxicity was observed. Despite no cytokine boosting was given, transient HSPC-NK cell persistence was clearly found in peripheral blood up to 21% until day 8, which was accompanied by augmented IL-15 plasma levels. Moreover, donor chimerism up to 3.5% was found in bone marrow. Interestingly, in vivo HSPC-NK cell maturation was observed, indicated by the rapid acquisition of CD16 and KIR expression, while expression of most activating receptors was sustained. Notably, two out of four patients with minimal residual disease (MRD) in bone marrow before infusion became MRD negative (<0.1%), which lasted for 6 months. Conclusions: These findings indicate that HSPC-NK cell adoptive transfer is a promising, potential "off-the-shelf" translational immunotherapy approach in AML.
- Received November 28, 2016.
- Revision received March 1, 2017.
- Accepted March 7, 2017.
- Copyright ©2017, American Association for Cancer Research.