New Applications for Bispecific Antibodies in Wound Healing (94.16)

Abstract

Abstract Bispecific antibodies (BiAbs) have potential to confer injury-specific targeting to cells for enhancing wound repair. Studies are designed to test BiAbs for their ability to direct recruitment and trafficking of specific cell populations (i.e. stem cells or macrophages) to sites of injury. A new series of BiAbs for wound repair applications have been chemically heteroconjugated: monoclonal antibodies (mAbs) for specific cell populations (i.e. F4/80 on macrophages, or c-kit on stem cells) were linked to mAbs against injury-associated antigens (i.e. VCAM, fibrinopeptide A). Heteroconjugation efficiency was measured by SDS-PAGE/densitometry, demonstrating final product composition of 66.75%, 58.76%, and 24.80% active heteroconjugates of F4/80xFibA, F4/80xVCAM, and cKitxVCAM, respectively. Specific BiAb binding to macrophage or stem cell populations was observed by flow cytometry. Functional BiAb binding was quantified in a novel biological assay. With these three distinct BiAbs successfully heteroconjugated and validated in vitro, studies are underway to test trafficking of BiAb-armed cells to injured tissue in murine models of wound repair: full thickness skin wounds and external muscle crush injury.