Abstract:PBMC derived from residual blood of the AMICUS and Trima Accel apheresis devices serve as an economic and easily accessible source for functional PBMCs with comparable quantity and quality to PBMCs derived from whole blood.
“…In this study we confirm and extend previous studies suggesting that PBMCs obtained from LRSCs are an adequate surrogate for the study of human leukocytes. Our data using paired PBMCs from LRSC and blood collected during the same procedure, show that there is high concordance in the relative counts of all major mononuclear subsets . This was also the case in the conventional T‐cell compartment, where CD4+ and CD8+ T cells at different stage of memory differentiation were found in similar percentages.…”
Section: Discussionsupporting
confidence: 71%
“…Blood banks apply universal leukoreduction to all blood products to reduce adverse events associated with the transfusion of blood products . Héma‐Québec's leukoreduced platelet concentrates are produced with apheresis instruments.…”
mentioning
confidence: 99%
“…LRSCs contain high numbers of peripheral blood mononuclear cells (PBMCs) and are a reliable source of human cells for research. As such, LRSCs are an alternative to peripheral blood collections or apheresis for the study of B cells, monocytes, dendritic cells (DCs), stem cells, and T cells . Regular platelet apheresis donors undergo extensive testing for transmissible diseases, are often well characterized in terms of human leukocyte antigen (HLA) typing as well as serostatus for common latent pathogens.…”
mentioning
confidence: 99%
“…B lood banks apply universal leukoreduction to all blood products to reduce adverse events associated with the transfusion of blood products. [1][2][3][4] Héma-Québec's leukoreduced platelet concentrates are produced with apheresis instruments. During the past year, more than 36,000 leukoreduced platelet concentrates were produced, generating as many leukoreduction system chambers (LRSCs), which were discarded at the end of the process.…”
mentioning
confidence: 99%
“…As such, LRSCs are an alternative to peripheral blood collections or apheresis for the study of B cells, monocytes, dendritic cells (DCs), stem cells, and T cells. 2,[5][6][7][8][9][10] Regular platelet apheresis donors undergo extensive testing for transmissible diseases, are often well characterized in terms of human leukocyte antigen (HLA) typing as well as serostatus for common latent pathogens. As such, PBMCs harvested from LRSCs following collection of platelets by apheresis may be exploitable as a safe source of PBMCs for therapeutic applications.…”
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.
“…In this study we confirm and extend previous studies suggesting that PBMCs obtained from LRSCs are an adequate surrogate for the study of human leukocytes. Our data using paired PBMCs from LRSC and blood collected during the same procedure, show that there is high concordance in the relative counts of all major mononuclear subsets . This was also the case in the conventional T‐cell compartment, where CD4+ and CD8+ T cells at different stage of memory differentiation were found in similar percentages.…”
Section: Discussionsupporting
confidence: 71%
“…Blood banks apply universal leukoreduction to all blood products to reduce adverse events associated with the transfusion of blood products . Héma‐Québec's leukoreduced platelet concentrates are produced with apheresis instruments.…”
mentioning
confidence: 99%
“…LRSCs contain high numbers of peripheral blood mononuclear cells (PBMCs) and are a reliable source of human cells for research. As such, LRSCs are an alternative to peripheral blood collections or apheresis for the study of B cells, monocytes, dendritic cells (DCs), stem cells, and T cells . Regular platelet apheresis donors undergo extensive testing for transmissible diseases, are often well characterized in terms of human leukocyte antigen (HLA) typing as well as serostatus for common latent pathogens.…”
mentioning
confidence: 99%
“…B lood banks apply universal leukoreduction to all blood products to reduce adverse events associated with the transfusion of blood products. [1][2][3][4] Héma-Québec's leukoreduced platelet concentrates are produced with apheresis instruments. During the past year, more than 36,000 leukoreduced platelet concentrates were produced, generating as many leukoreduction system chambers (LRSCs), which were discarded at the end of the process.…”
mentioning
confidence: 99%
“…As such, LRSCs are an alternative to peripheral blood collections or apheresis for the study of B cells, monocytes, dendritic cells (DCs), stem cells, and T cells. 2,[5][6][7][8][9][10] Regular platelet apheresis donors undergo extensive testing for transmissible diseases, are often well characterized in terms of human leukocyte antigen (HLA) typing as well as serostatus for common latent pathogens. As such, PBMCs harvested from LRSCs following collection of platelets by apheresis may be exploitable as a safe source of PBMCs for therapeutic applications.…”
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.
The expansion of T cells ex vivo is crucial for effective immunotherapy but currently limited by a lack of expansion approaches that closely mimic in vivo T cell activation. Taking inspiration from bottom‐up synthetic biology, a new synthetic cell technology is introduced based on dispersed liquid‐liquid phase‐separated droplet‐supported lipid bilayers (dsLBs) with tunable biochemical and biophysical characteristics, as artificial antigen presenting cells (aAPCs) for ex vivo T cell expansion. These findings obtained with the dsLB technology reveal three key insights: first, introducing laterally mobile stimulatory ligands on soft aAPCs promotes expansion of IL‐4/IL‐10 secreting regulatory CD8+ T cells, with a PD‐1 negative phenotype, less prone to immune suppression. Second, it is demonstrated that lateral ligand mobility can mask differential T cell activation observed on substrates of varying stiffness. Third, dsLBs are applied to reveal a mechanosensitive component in bispecific Her2/CD3 T cell engager‐mediated T cell activation. Based on these three insights, lateral ligand mobility, alongside receptor‐ and mechanosignaling, is proposed to be considered as a third crucial dimension for the design of ex vivo T cell expansion technologies.
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