Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation

Allogeneic hematopoietic cell transplantation (allo-HCT) is an efficacious and frequently the only treatment option for some hematological malignances. However, it often faces severe morbidities and/or mortalities due to graft versus host disease, and the severity of the conditioning regiment needed...

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Main Authors: Maite Alvarez, Antonio Pierini, Federico Simonetta, Jeanette Baker, Kristina Maas-Bauer, Toshihito Hirai, Robert S. Negrin
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2020.614250/full
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author Maite Alvarez
Maite Alvarez
Maite Alvarez
Maite Alvarez
Antonio Pierini
Federico Simonetta
Jeanette Baker
Kristina Maas-Bauer
Toshihito Hirai
Robert S. Negrin
author_facet Maite Alvarez
Maite Alvarez
Maite Alvarez
Maite Alvarez
Antonio Pierini
Federico Simonetta
Jeanette Baker
Kristina Maas-Bauer
Toshihito Hirai
Robert S. Negrin
author_sort Maite Alvarez
collection DOAJ
description Allogeneic hematopoietic cell transplantation (allo-HCT) is an efficacious and frequently the only treatment option for some hematological malignances. However, it often faces severe morbidities and/or mortalities due to graft versus host disease, and the severity of the conditioning regiment needed, that result in toxicity-related issues poorly tolerable for some patients. These shortcomings have led to the development of less aggressive alternatives like non-myeloablative (NMAC) or reduced-intensity conditioning regiments (RIC). However, these approaches tend to have an increase of cancer relapse and limited persistence of donor-specific chimerism. Thus, strategies that lead towards an accelerated and more durable donor engraftment are still needed. Here, we took advantage of the ability of host-derived unlicensed NK (UnLicNK) cells to favor donor cell engraftment during myeloablative allo-HCT, and evaluated if the adoptive transfer of this cell type can improve donor chimerism in NAMC settings. Indeed, the infusion of these cells significantly increased mixed chimerism in a sublethal allo-HCT mouse model, resulting in a more sustainable donor cell engraftment when compared to the administration of licensed NK cells or HCT controls. We observed an overall increase in the total number and proportion of donor B, NK and myeloid cells after UnLicNK cell infusion. Additionally, the extension and durability of donor chimerism was similar to the one obtained after the tolerogenic Tregs infusion. These results serve as the needed bases for the implementation of the adoptive transfer of UnLicNK cells to upgrade NMAC protocols and enhance allogeneic engraftment during HCT.
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spelling doaj.art-747e9f838f024c8089f0e82b0ec072f42022-12-21T23:24:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-01-011110.3389/fimmu.2020.614250614250Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell TransplantationMaite Alvarez0Maite Alvarez1Maite Alvarez2Maite Alvarez3Antonio Pierini4Federico Simonetta5Jeanette Baker6Kristina Maas-Bauer7Toshihito Hirai8Robert S. Negrin9Blood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, United StatesProgram for Immunology and Immunotherapy Department, Center for Applied Medical research (CIMA), Universidad de Navarra, Pamplona, SpainNavarra Institute for Health Research (IdiSNA), Pamplona, SpainCentro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, SpainBlood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, United StatesBlood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, United StatesBlood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, United StatesBlood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, United StatesBlood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, United StatesBlood and Marrow Transplantation, Stanford University School of Medicine, Stanford, CA, United StatesAllogeneic hematopoietic cell transplantation (allo-HCT) is an efficacious and frequently the only treatment option for some hematological malignances. However, it often faces severe morbidities and/or mortalities due to graft versus host disease, and the severity of the conditioning regiment needed, that result in toxicity-related issues poorly tolerable for some patients. These shortcomings have led to the development of less aggressive alternatives like non-myeloablative (NMAC) or reduced-intensity conditioning regiments (RIC). However, these approaches tend to have an increase of cancer relapse and limited persistence of donor-specific chimerism. Thus, strategies that lead towards an accelerated and more durable donor engraftment are still needed. Here, we took advantage of the ability of host-derived unlicensed NK (UnLicNK) cells to favor donor cell engraftment during myeloablative allo-HCT, and evaluated if the adoptive transfer of this cell type can improve donor chimerism in NAMC settings. Indeed, the infusion of these cells significantly increased mixed chimerism in a sublethal allo-HCT mouse model, resulting in a more sustainable donor cell engraftment when compared to the administration of licensed NK cells or HCT controls. We observed an overall increase in the total number and proportion of donor B, NK and myeloid cells after UnLicNK cell infusion. Additionally, the extension and durability of donor chimerism was similar to the one obtained after the tolerogenic Tregs infusion. These results serve as the needed bases for the implementation of the adoptive transfer of UnLicNK cells to upgrade NMAC protocols and enhance allogeneic engraftment during HCT.https://www.frontiersin.org/articles/10.3389/fimmu.2020.614250/fullUnlicensed NKallogeneic hematopoietic cell transplantationchimerasengraftmentnon-myeloablative conditioning regimen
spellingShingle Maite Alvarez
Maite Alvarez
Maite Alvarez
Maite Alvarez
Antonio Pierini
Federico Simonetta
Jeanette Baker
Kristina Maas-Bauer
Toshihito Hirai
Robert S. Negrin
Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation
Frontiers in Immunology
Unlicensed NK
allogeneic hematopoietic cell transplantation
chimeras
engraftment
non-myeloablative conditioning regimen
title Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation
title_full Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation
title_fullStr Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation
title_full_unstemmed Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation
title_short Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation
title_sort infusion of host derived unlicensed nk cells improves donor engraftment in non myeloablative allogeneic hematopoietic cell transplantation
topic Unlicensed NK
allogeneic hematopoietic cell transplantation
chimeras
engraftment
non-myeloablative conditioning regimen
url https://www.frontiersin.org/articles/10.3389/fimmu.2020.614250/full
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