Histamine-Succinyl-Glycine binding site (HSG binding site)

The Histamine-Succinyl-Glycine (HSG) binding site on the TF2 bispecific antibody is a specialized molecular recognition domain designed to bind the synthetic hapten HSG with high affinity (Sharkey et al., 2003, Cancer Res). TF2 is a trivalent bispecific antibody constructed via "Dock-and-Lock" (DNL) technology, comprising two humanized Fab fragments (hMN-14) targeting Carcinoembryonic Antigen (CEA) and one humanized Fab fragment (h679) targeting HSG (Goldenberg et al., 2008, J Nucl Med). This binding site is a critical component of pretargeted radioimmunotherapy (PRIT) and pretargeted immuno-PET imaging. In clinical applications, TF2 is administered first to saturate CEA-expressing tumor cells; subsequently, a small radiolabeled peptide containing HSG, such as IMP288, is injected. The radiolabeled peptide is rapidly captured by the Anti-HSG binding site on the tumor-bound TF2, while unbound peptide is quickly cleared through the kidneys, significantly improving the tumor-to-background radiation ratio compared to conventional radioimmunotherapy (Schoffelen et al., 2013, J Nucl Med). This approach minimizes radiation exposure to healthy tissues while maximizing the dose delivered to the tumor site.

Other names

h679 binding siteAnti-HSG paratopeHSG-hapten binding siteTF2 HSG-binding arm

The Anti-HSG binding site facilitates pretargeted radioimmunotherapy (PRIT) and imaging by acting as a high-affinity docking station for radiolabeled HSG-peptides after the bispecific antibody has localized to tumor-associated antigens such as Carcinoembryonic Antigen (CEA).