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Clin Cancer Res. 2017 Aug 1;23(15):4107-4118. doi: 10.1158/1078-0432.CCR-16-2981. Epub 2017 Mar 9.

Successful Transfer of Umbilical Cord Blood CD34+ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients.

Author information

1
Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands. harry.dolstra@radboudumc.nl.
2
Department of Laboratory Medicine - Laboratory of Hematology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
3
Department of Hematology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
4
Glycostem Therapeutics, Oss, the Netherlands.
5
Albert Schweitzer Hospital, Dordrecht, the Netherlands.
6
Medical Hospital Twente, Enschede, the Netherlands.
7
Department of Hematology, Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands.
8
Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands.
9
Department of Internal Medicine, Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands.

Abstract

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 a unique scalable NK-cell product generated ex vivo from CD34+ hematopoietic stem and progenitor cells (HSPC) 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 30 × 106/kg body weight) after lymphodepleting chemotherapy without cytokine boosting.Results: HSPC-NK cell products contained a median of 75% highly activated NK cells, with <1 × 104 T cells/kg and <3 × 105 B cells/kg body weight. HSPC-NK cells were well tolerated, and neither graft-versus-host disease nor toxicity was observed. Despite no cytokine boosting being given, transient HSPC-NK cell persistence was clearly found in peripheral blood up to 21% until day 8, which was accompanied by augmented IL15 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, 2 of 4 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. Clin Cancer Res; 23(15); 4107-18. ©2017 AACR.

PMID:
28280089
DOI:
10.1158/1078-0432.CCR-16-2981
[Indexed for MEDLINE]
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