Enhancement of adoptive T cell transfer with single low dose pretreatment of @entity632 or XXXX in @entity19 .

@entity1 @entity632 @entity10178 @entity1750 @entity5 @entity19 @entity13128 @entity1311 @entity1618 @entity523 @entity3105 @entity1611 @entity22663
UNASSIGNED: Ex vivo expansion of CD8+ T-cells has been a hindrance for the success of adoptive T cell transfer in clinic. Currently, preconditioning with chemotherapy is used to modulate the @entity1 immunity before ACT, however, the @entity5 microenvironment beneficial for transferring T cells may also be damaged. Here preconditioning with single low dose of @entity632 or @entity1311 combined with fewer CD8+ T-cells was investigated to verify whether the same therapeutic efficacy of ACT could be achieved. An E.G7/OT1 animal model that involved adoptive transfer of OVA-specific CD8+ T-cells transduced with a granzyme B promoter-driven firefly luciferase and @entity523 fluorescent fusion reporter gene was used to evaluate this strategy. The result showed that CD8+ T-cells were activated and sustained longer in @entity19 pretreated with one low-dose @entity3105 or Tax. Enhanced therapeutic efficacy was found in @entity3105 or Tax combined with 2x106 CD8+ T-cells and achieved the same level of @entity5 growth inhibition as that of 5x106 CD8+ T-cells group. Notably, reduced numbers of Tregs and myeloid derived suppressor cells were shown in combination groups. By contrast, the number of @entity5 -infiltrating cytotoxic T lymphocytes and IL-12 were increased. The NF-kB activity and immunosuppressive factors such as TGF-b, @entity22663 , @entity1750 , @entity1611 , @entity13128 , @entity10178 and @entity1618 were suppressed. This study demonstrates that preconditioning with single low dose @entity3105 or Tax and combined with two fifth of the original CD8+ T-cells could improve the @entity5 microenvironment via suppression of NF-kB and its related immunosuppressors, and activate more CD8+ T-cells which also stay longer.
