Anti-histamine-succinyl-glycine paratope on TF2 (Anti-HSG paratope)

The anti-HSG paratope on TF2 is a specialized antigen-binding site engineered to recognize the synthetic hapten histamine-succinyl-glycine (HSG). TF2 is a trivalent bispecific antibody (bsAb) produced via 'Dock-and-Lock' (DNL) technology, featuring two arms specific for carcinoembryonic antigen (CEA) and one arm containing the anti-HSG paratope derived from the h679 antibody clone (Sharkey et al., 2008, J Nucl Med). This system is designed for pre-targeted radioimmunotherapy (PRIT) and immuno-PET imaging, where the antibody is used to 'pre-target' tumor cells before the administration of a small-molecule radioactive payload (Goldenberg et al., 2012, J Control Release). By decoupling the slow-clearing antibody from the fast-clearing radionuclide, the anti-HSG paratope enables high tumor-to-background ratios and reduces radiation-induced toxicity to healthy organs like the bone marrow (Schoffelen et al., 2010, Eur J Nucl Med Mol Imaging). This technology is primarily investigated for the treatment and diagnosis of CEA-positive malignancies, including colorectal and medullary thyroid cancers.

Other names

h679 binding siteHSG-binding arm of TF2Anti-HSG Fab fragmentHistamine-succinyl-glycine binding site

The anti-HSG paratope serves as a high-affinity docking site for radiolabeled haptens in a multi-step pre-targeting strategy. The bispecific antibody TF2 first localizes to tumor-associated carcinoembryonic antigen (CEA). Once unbound TF2 clears from the circulation, a small, radiolabeled HSG-containing peptide (hapten) is administered, which rapidly binds to the anti-HSG paratope on the tumor-localized TF2, delivering radiation or imaging agents specifically to the tumor site (Sharkey et al., 2008, J Nucl Med; Goldenberg et al., 2012, J Control Release).