FLT3-directed BiTE molecules vs CAR T cells in AML: costimulatory signals mitigate T-cell exhaustion - PubMed

4 hours ago

FLT3 is a promising therapeutic target in AML with limited expression in healthy tissues.
FLT3-directed BiTE molecules and CAR T cells show potent cytotoxicity against AML cells but spare healthy cells.
CAR T cells maintain cytotoxic capacity and proliferative potential better than BiTE molecules over time.
In xenograft models, CAR T cells achieve superior tumor control and prolonged survival compared to BiTE-treated cells.
BiTE-treated T cells show an exhaustion-associated gene signature, while CAR T cells do not.
CD86-mediated costimulation enhances the antitumor activity of BiTE-redirected T cells both in vitro and in vivo.
The study highlights the importance of costimulatory signaling in sustaining T-cell-based therapies in AML.

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