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Fibroblast activation protein alpha (FAPα) chimeric antigen receptor (CAR) T cells are an investigational cell therapy designed to target FAPα, a protein highly expressed on cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) and on certain solid tumor cells. Developed using the proprietary Eumbody System, specific optimized clones such as FL12 utilize a single-chain variable fragment (scFv) with tuned binding affinity to mitigate trogocytosis—the unintended transfer of target antigens to the T cells—which can lead to T-cell exhaustion and target loss. The CAR construct typically incorporates a CD28 costimulatory domain and a CD3ζ signaling domain. By concurrently depleting immunosuppressive CAFs and targeting FAPα-positive tumor cells, this therapy aims to overcome physical and immunological barriers in the TME, demonstrating enhanced persistence and anti-tumor efficacy in preclinical models of glioblastoma and other CAF-rich solid malignancies.
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