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- W4313408013 abstract "Abstract After allogeneic stem cell transplantation, minor histocompatibility antigens (MiHAs), Wilms-Tumor 1 (WT1) antigen, and other peptides presented by host hematologic cancer (HC) cells can lead to the in vivo expansion of donor T cells crucial for the graft-versus-leukemia effect. While the specific ex vivo production of such leukemia-specific T cells represents an interesting treatment approach, the generation of these antigen-specific donor T cells represents a major challenge. We have developed a protocol enabling the infusion of monocyte derived dendritic cell (DC)-induced ex vivo expanded T cells specific for MiHAs, WT1 and other peptides that are preferentially expressed on hematologic cells for the treatment of relapsed HC patients. While it provides interesting results, our 42-day expansion protocol is costly and requires prolonged culture periods during which patient with HC could deteriorate rapidly. To accelerate T cell production, we compared DCs generated in 3 days (DC3) vs 9 days (DC9) using standard maturation cocktail and toll-like receptor agonist. DC3 showed small differences in expression of maturation/activation markers and a unique gene signature vs DC9. Importantly, the frequency of WT1-specific CD8 T cells, primed by DC3, was slightly higher than that in DC9 primed cultures. Upon restimulation, these DC3-primed-WT1-specific T cells expressed higher amounts of IFNγ, TNFα, and CD107a degranulation marker, and were cytotoxic against WT1-expressing autologous blast cells. Together, these data show that matured DC3 have a strong capacity to prime and expand functional anti-tumor antigen-specific CD8 T cells and thus offer most interesting features for ex vivo expansion of T cells for cancer immunotherapy." @default.
- W4313408013 created "2023-01-06" @default.
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- W4313408013 date "2022-05-01" @default.
- W4313408013 modified "2023-10-01" @default.
- W4313408013 title "Improved anti-tumor T cell generation using rapidly differentiated dendritic cells" @default.
- W4313408013 doi "https://doi.org/10.4049/jimmunol.208.supp.122.25" @default.
- W4313408013 hasPublicationYear "2022" @default.
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