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Enhanced Lymphodepletion Is Insufficient to Replace Exogenous IL2 or IL15 Therapy in Augmenting the Efficacy of Adoptively Transferred Effector CD8+ T Cells.


ABSTRACT: Effector CD8+ T cells conditioned with IL12 during activation mediate enhanced antitumor efficacy after adoptive transfer into lymphodepleted hosts; this is due in part to improved IL7 responsiveness. Therefore, we hypothesized that increasing the intensity or type of lymphodepletion would deplete more IL7-consuming host cells and improve the persistence and antitumor activity of IL12-conditioned CD8+ T cells. Using cyclophosphamide, fludarabine, and total body irradiation (TBI, 6 Gy) either individually or in combination, we found that combined lymphodepletion best enhanced T-cell engraftment in mice. This improvement was strongly related to the extent of leukopenia, as posttransfer levels of donor T cells inversely correlated to host cell counts after lymphodepletio

SUBMITTER: Johnson CB 

PROVIDER: S-EPMC6108084 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature