anti-CD38 scFv/Anti-DOTA scFv fusion protein CD38-SADA

A fusion protein composed of a single chain variable fragment (scFv) targeting the human cell surface glycoprotein and tumor-associated antigen (TAA) CD38, an scFv targeting the chelating agent 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and a self-assembling and disassembling (SADA) domain that can self-assemble from a monomeric polypeptide into tetrameric protein, that may be used as a pre-targeted radioimmunotherapeutic agent. Upon administration, anti-CD38 scFv/anti-DOTA scFv fusion protein CD38-SADA assembles in tetramers and the anti-CD38 scFv binds to CD38-expressing tumor cells. The unbound CD38-SADA is excreted. Upon administration of a DOTA-based radioactive payload, the anti-DOTA scFv binds to the DOTA moiety of the radioactive payload, and radiation is selectively delivered to tumor cells expressing CD38. CD38, a type II transmembrane glycoprotein, is present on various immune cells and hematologic malignancies; its expression has been correlated with poor prognosis.