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GrB-Fc-KS49 is a novel fully human recombinant fusion protein therapeutic designed for the treatment of breast cancer, specifically triple-negative breast cancer (TNBC). The construct consists of a human single-chain variable fragment (scFv) targeting epithelial membrane protein-2 (EMP2) fused to an immunoglobulin G (IgG) Fc domain and the cytotoxic serine protease granzyme B. EMP2 is highly expressed in over 75% of breast cancer patients and 100% of metastatic lesions, making it a viable target for directed therapy. Upon binding to EMP2 on the surface of tumor cells, the fusion protein is internalized, allowing granzyme B to enter the cytoplasm and induce apoptosis through caspase activation. Beyond direct cytotoxicity, GrB-Fc-KS49 initiates immunogenic cell death (ICD), leading to the release of damage-associated molecular patterns (DAMPs) such as HMGB1 and ATP. This secondary effect promotes an anti-tumor immune response by altering the tumor microenvironment, specifically increasing M1 macrophage recruitment and CD45+ immune cell infiltration.
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