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HB21(fv)PE40 (also known as ATFP) is a recombinant single-chain immunotoxin designed to target cells expressing the human transferrin receptor (TFRC/CD71). It is composed of the single-chain variable fragment (scFv) of the murine monoclonal antibody HB21 genetically fused to PE40, a 40 kDa truncated mutant of Pseudomonas exotoxin A that lacks its native cell-binding domain. Developed by the National Cancer Institute (NCI) in collaboration with academic institutions such as Johns Hopkins University, HB21(fv)PE40 binds specifically to TFRC, which is highly overexpressed in various malignancies, including breast cancer, ductal carcinoma in situ (DCIS), colorectal cancer, and pancreatic cancer. Upon binding, the immunotoxin is internalized via receptor-mediated endocytosis and trafficked to the cytosol, where the PE40 payload catalyzes the ADP-ribosylation and inactivation of eukaryotic translation elongation factor 2 (EEF2). This action halts protein synthesis, leading to apoptotic cell death. To mitigate systemic liver toxicity associated with systemic administration of TFRC-targeted agents, researchers have investigated localized routes of administration, such as intraductal injection for the treatment of DCIS.
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