anti-GD2 scFv/anti-DOTA scFv fusion protein GD2-SADA

A fusion protein composed of a single chain variable fragment (scFv) targeting the tumor-associated antigen (TAA) and disialoganglioside GD2, 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-GD2 scFv/anti-DOTA scFv fusion protein GD2-SADA assembles in tetramers and the anti-GD2 scFv binds to GD2-expressing tumor cells. The unbound GD2-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 GD2. GD2, a disialoganglioside with expression in normal tissues restricted primarily to the cerebellum and peripheral nerves, is commonly expressed at high levels on tumors of neuroectodermal origins such as melanomas and neuroblastomas.