GD2-specific antigen-binding fusion protein with SADA domain (GD2-SADA)

GD2-SADA is a recombinant bispecific fusion protein constructed for pretargeted radioimmunotherapy of GD2-expressing tumors. The molecule features a domain that binds specifically to the tumor-associated disialoganglioside GD2 (highly expressed in neuroblastoma, melanoma, sarcoma, and some other solid tumors) and a separate domain that binds the small-molecule chelator DOTA linked to the therapeutic radionuclide lutetium-177. In the first step, non-radioactive GD2-SADA is administered, homing to tumors by binding cell-surface GD2. Circulating, unbound GD2-SADA disassembles into smaller, renally-cleared units. In the next step, a radiolabeled 177Lu-DOTA compound is infused, which selectively binds to SADA pre-coated tumors, thus limiting systemic radiation exposure and improving the therapeutic index. This approach is under clinical investigation for several solid tumor types[1][3][5][7][9]. - The **SADA** (Self-Assembling and DisAssembling) domain provides the protein with the ability to multimerize for high-avidity tumor targeting and then monomerize for rapid clearance, reducing off-tumor toxicity[8]. - This modular approach is distinguished from conventional antibody therapies (like dinutuximab or naxitamab) by separating tumor binding from radionuclide delivery in time, enhancing selectivity and safety[7][9].

Other names

Anti-GD2 SADA fusion proteinGD2 SADA constructGD2 SADA bispecific fusion protein

Targeted radioimmunotherapy: The GD2-SADA fusion protein first binds to tumor-associated GD2, and then, in a subsequent step, the radiolabeled payload (177Lu-DOTA) is administered, which binds to the prelocalized fusion protein, delivering localized irradiation to tumor cells[1][3][5][7].