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αvβ3.28z CAR-T cells are an experimental second-generation chimeric antigen receptor (CAR) T-cell therapy designed to target the integrin αvβ3 complex. This integrin is highly expressed on the surface of high-grade gliomas, including glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG), as well as their associated vasculature, while maintaining minimal expression in normal tissues. The CAR construct incorporates a single-chain variable fragment (scFv) specific for αvβ3, a CD28 co-stimulatory domain, and a CD3ζ signaling domain. Developed by researchers at the University of Virginia, these cells have demonstrated potent in vitro cytotoxicity and robust anti-tumor responses in orthotopic mouse models of DIPG and GBM. Compared to 4-1BB-based versions (αvβ3.BBz), the CD28-containing αvβ3.28z variant exhibits faster expansion kinetics but has shown potential toxicity concerns in preclinical models, leading to the prioritization of the BBz variant for initial clinical trials.
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