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YTH25.4 is an unconjugated rat monoclonal antibody of the IgG2b subclass that specifically targets the human CD45 antigen (also known as leukocyte common antigen or PTPRC), a transmembrane protein expressed on all hematopoietic cells except mature erythrocytes and platelets. Developed by Herman Waldmann and colleagues at the University of Cambridge, YTH25.4 binds to an epitope common to all CD45 isoforms. It is typically administered in a synergistic combination with another anti-CD45 antibody, YTH54.12, to recruit host lytic effector mechanisms such as complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Clinically, this pair has been investigated as a non-myeloablative or reduced-intensity conditioning agent for patients undergoing hematopoietic stem cell transplantation (HSCT) for hematologic malignancies like acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Additionally, it has been studied as a lymphodepleting agent to facilitate the expansion of adoptively transferred EBV-specific cytotoxic T lymphocytes in patients with nasopharyngeal carcinoma. While effective at depleting lymphoid and myeloid cells while sparing early marrow progenitors, its clinical utility is limited by its rat origin, which can induce human anti-rat antibody (HARA) responses upon repeated administration.
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