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

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”...

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Bibliographic Details
Published in:Transfusion (Philadelphia, Pa.) Pa.), 2019-04, Vol.59 (4), p.1300-1311
Main Authors: Boudreau, Gabrielle, Carli, Cédric, Lamarche, Caroline, Rulleau, Caroline, Bonnaure, Guillaume, Néron, Sonia, Delisle, Jean‐Sébastien
Format: Article
Language:English
Subjects:
Antibodies
Autografts
Blood
CD28 antigen
CD3 antigen
Cell Line
Cell lines
Cellular manufacture
Chambers
Cryopreservation
Cytomegalovirus
Cytomegalovirus - immunology
Dendritic cells
Dendritic Cells - immunology
Humans
Immunotherapy
Immunotherapy, Adoptive - methods
L-selectin
Leukocyte Reduction Procedures - methods
Leukocytes (mononuclear)
Lymphocytes
Lymphocytes T
Manufacturing
Monocytes
Morbidity
Peptides
Peripheral blood mononuclear cells
Phenotypes
T-Lymphocytes - immunology
Transplantation
Transplants & implants
Viruses
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Summary: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.
ISSN:0041-1132
1537-2995
DOI:10.1111/trf.15121