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...

Descripción completa

Detalles Bibliográficos
Autores: Álvarez, M. (Maite)|||/items/869c2b2f-e806-47ac-8d76-303de908d205, Pierini, A. (Antonio)|||/items/79566a9b-795e-49b6-906e-e4554bdc08da, Simonetta, F. (Federico)|||/items/3b4c58e5-39f2-4e62-865a-5dce5e6fcfc2, Baker, J. (Jeanette)|||/items/f6bd798d-1930-4ab2-a8c5-56b93163634a, Maas-Bauer, K. (Kristina)|||/items/8539a341-88d6-490e-bc4c-19d9b53140c0, Hirai, T. (Toshihito)|||/items/fb7ad87b-2b23-45e3-9092-363b0967102e, Negrin, R.S. (Robert S.)|||/items/107c1df4-b0d3-42e7-a7fe-5b36de38c156
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/115644
Acceso en línea:https://hdl.handle.net/10171/115644
Access Level:acceso abierto
Palabra clave:Unlicensed NK
Allogeneic hematopoietic cell transplantation
Chimeras
Engraftment
Non-myeloablative conditioning regimen
id ES_828ecd3676d425cdc4ebda8eda11f3da
oai_identifier_str oai:dadun.unav.edu:10171/115644
network_acronym_str ES
network_name_str España
repository_id_str
spelling Infusion of host-derived unlicensed NK cells improves donor engraftment in non-myeloablative allogeneic hematopoietic cell transplantationÁlvarez, M. (Maite)|||/items/869c2b2f-e806-47ac-8d76-303de908d205Pierini, A. (Antonio)|||/items/79566a9b-795e-49b6-906e-e4554bdc08daSimonetta, F. (Federico)|||/items/3b4c58e5-39f2-4e62-865a-5dce5e6fcfc2Baker, J. (Jeanette)|||/items/f6bd798d-1930-4ab2-a8c5-56b93163634aMaas-Bauer, K. (Kristina)|||/items/8539a341-88d6-490e-bc4c-19d9b53140c0Hirai, T. (Toshihito)|||/items/fb7ad87b-2b23-45e3-9092-363b0967102eNegrin, R.S. (Robert S.)|||/items/107c1df4-b0d3-42e7-a7fe-5b36de38c156Unlicensed NKAllogeneic hematopoietic cell transplantationChimerasEngraftmentNon-myeloablative conditioning regimenAllogeneic 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 Research FoundationDadun. Depósito Académico Digital Universidad de Navarra20212021-01-0120212021-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/115644reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/1156442026-06-21T12:47:57Z
dc.title.none.fl_str_mv 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
spellingShingle Infusion of host-derived unlicensed NK cells improves donor engraftment in non-myeloablative allogeneic hematopoietic cell transplantation
Álvarez, M. (Maite)|||/items/869c2b2f-e806-47ac-8d76-303de908d205
Unlicensed NK
Allogeneic hematopoietic cell transplantation
Chimeras
Engraftment
Non-myeloablative conditioning regimen
title_short 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_sort Infusion of host-derived unlicensed NK cells improves donor engraftment in non-myeloablative allogeneic hematopoietic cell transplantation
dc.creator.none.fl_str_mv Álvarez, M. (Maite)|||/items/869c2b2f-e806-47ac-8d76-303de908d205
Pierini, A. (Antonio)|||/items/79566a9b-795e-49b6-906e-e4554bdc08da
Simonetta, F. (Federico)|||/items/3b4c58e5-39f2-4e62-865a-5dce5e6fcfc2
Baker, J. (Jeanette)|||/items/f6bd798d-1930-4ab2-a8c5-56b93163634a
Maas-Bauer, K. (Kristina)|||/items/8539a341-88d6-490e-bc4c-19d9b53140c0
Hirai, T. (Toshihito)|||/items/fb7ad87b-2b23-45e3-9092-363b0967102e
Negrin, R.S. (Robert S.)|||/items/107c1df4-b0d3-42e7-a7fe-5b36de38c156
author Álvarez, M. (Maite)|||/items/869c2b2f-e806-47ac-8d76-303de908d205
author_facet Álvarez, M. (Maite)|||/items/869c2b2f-e806-47ac-8d76-303de908d205
Pierini, A. (Antonio)|||/items/79566a9b-795e-49b6-906e-e4554bdc08da
Simonetta, F. (Federico)|||/items/3b4c58e5-39f2-4e62-865a-5dce5e6fcfc2
Baker, J. (Jeanette)|||/items/f6bd798d-1930-4ab2-a8c5-56b93163634a
Maas-Bauer, K. (Kristina)|||/items/8539a341-88d6-490e-bc4c-19d9b53140c0
Hirai, T. (Toshihito)|||/items/fb7ad87b-2b23-45e3-9092-363b0967102e
Negrin, R.S. (Robert S.)|||/items/107c1df4-b0d3-42e7-a7fe-5b36de38c156
author_role author
author2 Pierini, A. (Antonio)|||/items/79566a9b-795e-49b6-906e-e4554bdc08da
Simonetta, F. (Federico)|||/items/3b4c58e5-39f2-4e62-865a-5dce5e6fcfc2
Baker, J. (Jeanette)|||/items/f6bd798d-1930-4ab2-a8c5-56b93163634a
Maas-Bauer, K. (Kristina)|||/items/8539a341-88d6-490e-bc4c-19d9b53140c0
Hirai, T. (Toshihito)|||/items/fb7ad87b-2b23-45e3-9092-363b0967102e
Negrin, R.S. (Robert S.)|||/items/107c1df4-b0d3-42e7-a7fe-5b36de38c156
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Unlicensed NK
Allogeneic hematopoietic cell transplantation
Chimeras
Engraftment
Non-myeloablative conditioning regimen
topic Unlicensed NK
Allogeneic hematopoietic cell transplantation
Chimeras
Engraftment
Non-myeloablative conditioning regimen
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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/115644
url https://hdl.handle.net/10171/115644
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Research Foundation
publisher.none.fl_str_mv Frontiers Research Foundation
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412054850338816
score 15.811543