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

The Histamine-Succinyl-Glycine (HSG)-binding domain is an engineered antibody fragment, most commonly derived from the humanized h679 antibody, which exhibits high affinity for the synthetic hapten HSG (Sharkey et al., 2003, PubMed: 12615687). This domain is a foundational element of the 'Dock-and-Lock' (DNL) platform used to create bispecific antibodies (BsAbs) for pre-targeted radioimmunotherapy and imaging (Goldenberg et al., 2012, PubMed: 22407838). In this therapeutic strategy, the BsAb—possessing one arm for a tumor-associated antigen and the HSG-binding domain for the other—is administered first to localize at the tumor site. After the BsAb has cleared from the circulation, a small, HSG-labeled peptide carrying a diagnostic or therapeutic payload (such as 177Lu or 90Y) is administered, which then binds rapidly to the HSG-binding domain on the tumor (Rossi et al., 2006, PubMed: 16707738). This mechanism allows for high tumor-to-background ratios, reducing systemic radiation exposure compared to directly labeled antibodies. The HSG-binding domain essentially functions as a synthetic receptor, enabling the precise delivery of various payloads to malignant tissues (Sharkey et al., 2005, PubMed: 16144925). It has been extensively studied in clinical trials for the treatment of colorectal, pancreatic, and medullary thyroid cancers using constructs like TF2 and TF10 (Schoffelen et al., 2013, PubMed: 23303603).

Other names

h679anti-HSG scFvanti-HSG Fab679 antibody domainHistamine-Succinyl-Glycine-binding arm

Pre-targeting