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

Harry Dolstra*, Mieke W. H. Roeven, Jan Spanholtz, Basav N. Hangalapura, Marleen Tordoir, Frans Maas, Marij Leenders, Fenna Bohme, Nina Kok, Carel Trilsbeek, Jos Paardekooper, Anniek B. van der Waart, Peter E. Westerweel, Tjeerd J. F. Snijders, Jan Cornelissen, Gerard Bos, Hans F. M. Pruijt, Aniek O. de Graaf, Bert A. van der Reijden, Joop H. JansenArnold van der Meer, Gerwin Huls, Jeannette Cany, Frank Preijers, Nicole M. A. Blijlevens, Nicolaas M. Schaap

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

83 Citations (Web of Science)

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-inhuman 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 x 10(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

Conclusions: These findings indicate that HSPC-NK cell adoptive transfer is a promising, potential "off-the-shelf" translational immunotherapy approach in AML. (C) 2017 AACR.

Original languageEnglish
Pages (from-to)4107-4118
Number of pages12
JournalClinical Cancer Research
Volume23
Issue number15
DOIs
Publication statusPublished - 1 Aug 2017

Keywords

  • NATURAL-KILLER-CELLS
  • REGULATORY T-CELLS
  • IN-VIVO EXPANSION
  • REDUCED-INTENSITY
  • LYMPHODEPLETING CHEMOTHERAPY
  • CONDITIONING REGIMEN
  • COMPLETE REMISSION
  • WORKING PARTY
  • TRANSPLANTATION
  • CANCER

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