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. Jansen; Arnold van der Meer; Gerwin Huls; Jeannette Cany; Frank Preijers; Nicole M. A. Blijlevens; Nicolaas M. Schaap

doi:10.1158/1078-0432.CCR-16-2981

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 journal › Article › Academic › peer-review

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

Original language	English
Pages (from-to)	4107-4118
Number of pages	12
Journal	Clinical Cancer Research
Volume	23
Issue number	15
DOIs	https://doi.org/10.1158/1078-0432.CCR-16-2981
Publication status	Published - 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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10.1158/1078-0432.CCR-16-2981

Cite this

Dolstra, H., Roeven, M. W. H., Spanholtz, J., Hangalapura, B. N., Tordoir, M., Maas, F., Leenders, M., Bohme, F., Kok, N., Trilsbeek, C., Paardekooper, J., van der Waart, A. B., Westerweel, P. E., Snijders, T. J. F., Cornelissen, J., Bos, G., Pruijt, H. F. M., de Graaf, A. O., van der Reijden, B. A., ... Schaap, N. M. (2017). Successful Transfer of Umbilical Cord Blood CD34⁺ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients. Clinical Cancer Research, 23(15), 4107-4118. https://doi.org/10.1158/1078-0432.CCR-16-2981

@article{6cb6c5f31a7448069ede58851fb8de2a,

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

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

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

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

year = "2017",

month = aug,

day = "1",

doi = "10.1158/1078-0432.CCR-16-2981",

language = "English",

volume = "23",

pages = "4107--4118",

journal = "Clinical Cancer Research",

issn = "1078-0432",

publisher = "American Association for Cancer Research Inc.",

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Dolstra, H, Roeven, MWH, Spanholtz, J, Hangalapura, BN, Tordoir, M, Maas, F, Leenders, M, Bohme, F, Kok, N, Trilsbeek, C, Paardekooper, J, van der Waart, AB, Westerweel, PE, Snijders, TJF, Cornelissen, J, Bos, G, Pruijt, HFM, de Graaf, AO, van der Reijden, BA, Jansen, JH, van der Meer, A, Huls, G, Cany, J, Preijers, F, Blijlevens, NMA & Schaap, NM 2017, 'Successful Transfer of Umbilical Cord Blood CD34⁺ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients', Clinical Cancer Research, vol. 23, no. 15, pp. 4107-4118. https://doi.org/10.1158/1078-0432.CCR-16-2981

TY - JOUR

T1 - Successful Transfer of Umbilical Cord Blood CD34+ Hematopoietic Stem and Progenitor-derived NK Cells in Older Acute Myeloid Leukemia Patients

AU - Dolstra, Harry

AU - Roeven, Mieke W. H.

AU - Spanholtz, Jan

AU - Hangalapura, Basav N.

AU - Tordoir, Marleen

AU - Maas, Frans

AU - Leenders, Marij

AU - Bohme, Fenna

AU - Kok, Nina

AU - Trilsbeek, Carel

AU - Paardekooper, Jos

AU - van der Waart, Anniek B.

AU - Westerweel, Peter E.

AU - Snijders, Tjeerd J. F.

AU - Cornelissen, Jan

AU - Bos, Gerard

AU - Pruijt, Hans F. M.

AU - de Graaf, Aniek O.

AU - van der Reijden, Bert A.

AU - Jansen, Joop H.

AU - van der Meer, Arnold

AU - Huls, Gerwin

AU - Cany, Jeannette

AU - Preijers, Frank

AU - Blijlevens, Nicole M. A.

AU - Schaap, Nicolaas M.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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, withConclusions: These findings indicate that HSPC-NK cell adoptive transfer is a promising, potential "off-the-shelf" translational immunotherapy approach in AML. (C) 2017 AACR.

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

KW - NATURAL-KILLER-CELLS

KW - REGULATORY T-CELLS

KW - IN-VIVO EXPANSION

KW - REDUCED-INTENSITY

KW - LYMPHODEPLETING CHEMOTHERAPY

KW - CONDITIONING REGIMEN

KW - COMPLETE REMISSION

KW - WORKING PARTY

KW - TRANSPLANTATION

KW - CANCER

U2 - 10.1158/1078-0432.CCR-16-2981

DO - 10.1158/1078-0432.CCR-16-2981

M3 - Article

C2 - 28280089

SN - 1078-0432

VL - 23

SP - 4107

EP - 4118

JO - Clinical Cancer Research

JF - Clinical Cancer Research

IS - 15

ER -