Natural Killer Cell Homing and Persistence in the Bone Marrow after Adoptive Immunotherapy Correlates with Better Leukemia Control

Bartosz J Grzywacz; Laura Moench; David H McKenna; Katelyn M Tessier; Veronika Bachanova; Sarah A Cooley; Jeffrey S Miller; Elizabeth L Courville

doi:10.1097/CJI.0000000000000250

Natural Killer Cell Homing and Persistence in the Bone Marrow after Adoptive Immunotherapy Correlates with Better Leukemia Control

Bartosz J Grzywacz, Laura Moench, David H McKenna, Katelyn M Tessier, Veronika Bachanova, Sarah A Cooley, Jeffrey S Miller, Elizabeth L Courville

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

Cellular immunotherapy using allogeneic natural killer (NK) cells may overcome chemotherapy-refractory acute myeloid leukemia. Our goal was to document NK cell homing/persistence in the bone marrow following adoptive immunotherapy. Our cohort included 109 patients who received NK cell therapy for refractory acute myeloid leukemia following lymphodepleting conditioning +/-denileukin diftitox, +/-low-dose total body irradiation. We evaluated the NK cell density in bone marrow core biopsies performed an average of 14 days after NK cell transfer using a CD56 immunohistochemical stain. The NK cell density in core biopsies showed only moderate correlation with NK cell percentage in bone marrow aspirates evaluated by flow cytometry (r s =0.48) suggesting that distribution of CD56 + cells in the bone marrow niche offers unique insight into NK cell homing. Better leukemia control was associated with increased NK cell density, such that patients with <5% blasts had a higher NK cell density (P=0.01). As well, NK cell density above the median of reference group was significantly associated with morphologic remission of leukemia (P=0.01). Moreover, the NK cell density varied significantly between conditioning protocols. Our findings suggest that the use of low-dose irradiation or CD25-targeting immunocytokine (denileukin diftitox, IL2DT) as part of conditioning results in increased NK cell homing/persistence in the bone marrow. These novel results will help guide future immunotherapy with NK cells.

Original language	English (US)
Pages (from-to)	65-72
Number of pages	8
Journal	Journal of Immunotherapy
Volume	42
Issue number	2
DOIs	https://doi.org/10.1097/CJI.0000000000000250
State	Published - Feb 1 2019

Bibliographical note

Funding Information:
University of Minnesota Molecular and Cellular Therapeutics Facility (PACT Contract #HHSN268201000008C); NIH P30CA77598 utilizing the Translational Therapy Laboratory Shared Resource of the Masonic Cancer Center, University of Minnesota; Children’s Cancer Research Fund, Leukemia Research Fund, and American Cancer Society, NIH P01 CA111412, and P01 CA65493. Research reported in this publication was supported by NIH grant P30CA77598 utilizing the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota and by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
Supported in part by the Production Assistance for Cellular Therapies (PACT) program from NIH/NHLBI at

Publisher Copyright:
© 2018 Wolters Kluwer Health, Inc. All rights reserved.

Keywords

CD56
NK cells
acute myeloid leukemia
bone marrow
immunotherapy

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/CJI.0000000000000250

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365204

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title = "Natural Killer Cell Homing and Persistence in the Bone Marrow after Adoptive Immunotherapy Correlates with Better Leukemia Control",

abstract = "Cellular immunotherapy using allogeneic natural killer (NK) cells may overcome chemotherapy-refractory acute myeloid leukemia. Our goal was to document NK cell homing/persistence in the bone marrow following adoptive immunotherapy. Our cohort included 109 patients who received NK cell therapy for refractory acute myeloid leukemia following lymphodepleting conditioning +/-denileukin diftitox, +/-low-dose total body irradiation. We evaluated the NK cell density in bone marrow core biopsies performed an average of 14 days after NK cell transfer using a CD56 immunohistochemical stain. The NK cell density in core biopsies showed only moderate correlation with NK cell percentage in bone marrow aspirates evaluated by flow cytometry (r s =0.48) suggesting that distribution of CD56 + cells in the bone marrow niche offers unique insight into NK cell homing. Better leukemia control was associated with increased NK cell density, such that patients with <5% blasts had a higher NK cell density (P=0.01). As well, NK cell density above the median of reference group was significantly associated with morphologic remission of leukemia (P=0.01). Moreover, the NK cell density varied significantly between conditioning protocols. Our findings suggest that the use of low-dose irradiation or CD25-targeting immunocytokine (denileukin diftitox, IL2DT) as part of conditioning results in increased NK cell homing/persistence in the bone marrow. These novel results will help guide future immunotherapy with NK cells.",

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author = "Grzywacz, {Bartosz J} and Laura Moench and McKenna, {David H} and Tessier, {Katelyn M} and Veronika Bachanova and Cooley, {Sarah A} and Miller, {Jeffrey S} and Courville, {Elizabeth L}",

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Natural Killer Cell Homing and Persistence in the Bone Marrow after Adoptive Immunotherapy Correlates with Better Leukemia Control

Abstract

Bibliographical note

Keywords

UN SDGs

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