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...
| Autores: | , , , , , , |
|---|---|
| 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 |
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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 |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 |
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openAccess |
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application/pdf |
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Frontiers Research Foundation |
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Frontiers Research Foundation |
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reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra instname:Universidad de Navarra |
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Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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Dadun. Depósito Académico Digital de la Universidad de Navarra |
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15.811543 |