Histamine-succinyl-glycine hapten (HSG) recognized by TF2 bispecific antibody (HSG)

Histamine-succinyl-glycine (HSG) is a small synthetic pseudo-peptide hapten employed in antibody–hapten pretargeting systems. TF2 is a humanized tri-Fab bispecific antibody constructed via Dock-and-Lock that contains two anti-CEACAM5 Fab arms and one anti-HSG Fab arm. After TF2 localizes to CEACAM5-positive tumors, a radiolabeled bivalent HSG-peptide (e.g., IMP288) is administered; its two HSG moieties confer affinity enhancement binding to TF2 at tumor sites and it clears rapidly from blood, yielding high tumor-to-background imaging and facilitating radioimmunotherapy. Clinical and preclinical studies have demonstrated feasibility, optimization of dosing intervals, and safety of the TF2/IMP288 system in CEACAM5-positive colorectal cancer models and patients.

Other names

histamine–succinyl–glycineHSG haptendi-HSG (when present bivalently in peptides such as IMP288)

Pretargeting: administer TF2 (anti-CEACAM5 × anti-HSG) to bind tumor CEACAM5, then inject a rapidly clearing radiolabeled bivalent HSG-peptide (e.g., IMP288) that binds TF2 at the tumor via affinity enhancement from bivalency, improving tumor uptake and contrast for PET/RIT.