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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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Autores principales: Alvarez, Maite, Pierini, Antonio, Simonetta, Federico, Baker, Jeanette, Maas-Bauer, Kristina, Hirai, Toshihito, Negrin, Robert S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817981/
https://www.ncbi.nlm.nih.gov/pubmed/33488624
http://dx.doi.org/10.3389/fimmu.2020.614250
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author Alvarez, Maite
Pierini, Antonio
Simonetta, Federico
Baker, Jeanette
Maas-Bauer, Kristina
Hirai, Toshihito
Negrin, Robert S.
author_facet Alvarez, Maite
Pierini, Antonio
Simonetta, Federico
Baker, Jeanette
Maas-Bauer, Kristina
Hirai, Toshihito
Negrin, Robert S.
author_sort Alvarez, Maite
collection PubMed
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 pubmed-78179812021-01-22 Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation Alvarez, Maite Pierini, Antonio Simonetta, Federico Baker, Jeanette Maas-Bauer, Kristina Hirai, Toshihito Negrin, Robert S. Front Immunol Immunology 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. Frontiers Media S.A. 2021-01-07 /pmc/articles/PMC7817981/ /pubmed/33488624 http://dx.doi.org/10.3389/fimmu.2020.614250 Text en Copyright © 2021 Alvarez, Pierini, Simonetta, Baker, Maas-Bauer, Hirai and Negrin http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Alvarez, Maite
Pierini, Antonio
Simonetta, Federico
Baker, Jeanette
Maas-Bauer, Kristina
Hirai, Toshihito
Negrin, Robert S.
Infusion of Host-Derived Unlicensed NK Cells Improves Donor Engraftment in Non-Myeloablative Allogeneic Hematopoietic Cell Transplantation
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817981/
https://www.ncbi.nlm.nih.gov/pubmed/33488624
http://dx.doi.org/10.3389/fimmu.2020.614250
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