Definition

: An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 kappa (IgG1k) monoclonal antibody directed against the tumor-associated antigen (TAA) human epidermal growth factor receptor 2 (EGFR2; HER2; ErbB2) conjugated, through a cleavable linker, to the cytotoxic agent eribulin, a synthetic, macrocyclic ketone analogue of halichondrin B, with potential antineoplastic activity. Upon administration of anti-HER2 ADC BB-1701, the anti-HER2 monoclonal antibody moiety targets and binds to HER2 expressed on tumor cells. Upon binding and internalization, the linker is cleaved by the lysosomal protease cathepsin B. The unconjugated eribulin targets and binds to the vinca domain of tubulin and inhibits both the polymerization of tubulin and the assembly of microtubules. This inhibits mitotic spindle assembly, induces cell cycle arrest at G2/M phase, and results in apoptosis of HER2-expressing tumor cells. In addition, BB-1701 induces a potent bystander effect in neighboring tumor cells and immunogenic cell death (ICD). HER2, a receptor tyrosine kinase that is mutated or overexpressed in many tumor cell types, plays an important role in tumor cell proliferation and tumor vascularization.