vobramitamab duocarmazine

An antibody-drug conjugate (ADC) comprised of vobamitamab, an anti-B7-homolog 3 (B7-H3, CD276) humanized immunoglobulin G1 (IgG1)/kappa monoclonal antibody, conjugated to the cleavable linker-duocarmycin payload duocarmazine (valine-citrulline-seco duocarmycin hydroxybenzamide azaindole; vc-seco-DUBA), with potential antineoplastic activity. Upon administration of vobramitamab duocarmazine, vobramitamab specifically targets and binds to the cell surface antigen B7-H3, leading to internalization of the ADC by B7-H3-expressing tumor cells. The vc linker is cleaved inside the tumor cell by proteases, thereby releasing the duocarmycin payload. Duocarmycin binds to the minor groove of DNA, alkylates adenine at the N3 position, and induces cell death. B7-H3, a type I transmembrane protein and a member of the B7 co-stimulatory protein superfamily, is overexpressed on certain tumor cell types and on various immune cells but is minimally expressed by normal human tissues. B7-H3 is a negative regulator of T-cell activation and its overexpression plays a key role in immuno-evasion, tumor cell invasion and metastasis, and its expression is correlated with poor prognosis.