期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.614250
关键词
Unlicensed NK; allogeneic hematopoietic cell transplantation; chimeras; engraftment; non-myeloablative conditioning regimen
类别
资金
- National Institute of Health [RO1CA125276, P01CA049605]
- AACR-Millennium Fellowship in Lymphoma Research [1540-38-ALVA]
- ASBMT New Investigator Award
- Marie Sklodowska-Curie fellowship [CINK 746985]
- Spanish Association Against Cancer's Investigator grant (2019 AECC Investigator)
- Geneva University Hospitals
- Swiss Cancer League
- Fondation Genevoise de bienfaisance Valeria Rossi di Montelera
- Dubois-FerriereDinu-Lipatti Foundation
- German Cancer Aid
- FACSAria II (BD Bioscience) [S10RR025518-01]
Allogeneic hematopoietic cell transplantation is an effective treatment option for hematological malignancies, but often results in severe toxicities. Less aggressive alternatives like NMAC and RIC have limitations including increased cancer relapse and limited persistence of donor chimerism. Strategies for accelerated and more durable donor engraftment are still needed.
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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