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CAR.B7H3.CD28.OX40 is an experimental third-generation chimeric antigen receptor (CAR) T-cell therapy designed to target B7-H3 (CD276), an immune checkpoint molecule overexpressed in various cancers, including acute myeloid leukemia (AML). The construct incorporates a novel B7-H3-specific single-chain variable fragment (scFv) and utilizes a combination of CD28 and OX40 co-stimulatory domains to enhance T-cell activation, proliferation, and persistence. Preclinical studies conducted by researchers at Bambino Gesù Children's Hospital and collaborating institutions have demonstrated potent anti-leukemic activity in vitro and in vivo, effectively eradicating B7-H3-positive AML cells and improving survival in xenograft mouse models. The dual co-stimulation provided by CD28 and OX40 is intended to optimize the metabolic fitness and long-term efficacy of the CAR T cells compared to second-generation designs.
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