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The anti-folate receptor alpha single-chain variable fragment-granzyme B fusion protein is an experimental recombinant fusion protein designed for the targeted treatment of FOLRa-positive malignancies, such as ovarian and breast cancers. Developed by researchers at the MD Anderson Cancer Center and supported by the Clayton Foundation for Research, this therapeutic candidate utilizes a single-chain variable fragment (scFv) to specifically bind to Folate Receptor Alpha (FOLRa) on the surface of tumor cells. Upon internalization, the cytotoxic payload—human granzyme B—is released into the cytosol, where it induces apoptosis by activating caspases and cleaving pro-apoptotic proteins like Bid. A distinguishing feature of this construct is its ability to induce immunogenic cell death (ICD), evidenced by the release of damage-associated molecular patterns (DAMPs) such as HMGB1, ATP, and Annexin A1. This dual mechanism of action aims to provide both direct tumor cell killing and a secondary immune-mediated bystander effect against antigen-negative or resistant tumor cells within the microenvironment.
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