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Transfusion. 2019 Apr;59(4):1300-1311. doi: 10.1111/trf.15121. Epub 2018 Dec 27.

Leukoreduction system chambers are a reliable cellular source for the manufacturing of T-cell therapeutics.

Author information

1
Centre de Recherche de l'Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada.
2
Medical Affairs and Innovation, Héma-Québec, Québec, Québec, Canada.
3
Department of Biochemistry, Microbiology and Bio-informatics, Université Laval, Québec, Québec, Canada.
4
Hematology-Oncology Division, Hôpital Maisonneuve-Rosemont, Montréal, Québec, Canada.
5
Department of Medicine, Université de Montréal, Montreal, Québec, Canada.

Abstract

BACKGROUND:

Following solid organ or hematopoietic cell transplantation, refractory opportunistic viral reactivations are a significant cause of morbidity and mortality but can effectively be controlled by virus-specific T-cell transfer. Among effective and safe strategies is the use of "third-party" (neither from the transplant donor nor recipient) virus-specific T cells that can be manufactured from healthy donors and used as "off-the-shelf" therapies. Leukoreduction system chambers (LRSCs), recovered after routine plateletpheresis, were evaluated as a potential source of peripheral blood mononuclear cells (PBMCs) for the manufacturing of clinical-scale virus-specific T cell.

STUDY DESIGN AND METHODS:

PBMCs from the same donors obtained either from LRSCs or peripheral blood were compared, focusing on T-cell function and phenotype as well as the potential to generate cytomegalovirus (CMV)-specific T-cell lines from both CMV seropositive and seronegative donors.

RESULTS:

PBMCs from both sources were comparable except for a transient downregulation of CD62L expression on freshly extracted PBMCs from LRSCs. Both nonspecific stimulation using anti-CD3/CD28 antibodies and CMV peptides revealed that LRSCs or blood T cells were equivalent in terms of expansion, differentiation, and function. Moreover, PBMCs from LRSCs can be used to generate autologous monocyte-derived dendritic cells to prime and expand CMV-specific T cells from seronegative donors.

CONCLUSION:

LRSCs are a reliable source of PBMCs for the generation of virus-specific T cells for immunotherapy. These findings have implications for the development of third-party therapeutic T-cell products from well-characterized blood product donors.

PMID:
30589447
DOI:
10.1111/trf.15121

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