Unnatural Amino Acid Antibody Conjugates as Next Generation Biologics

Abstract

Trastuzumab represents a monoclonal antibody therapeutic with substantial clinical benefit, but tumors ultimately evolve resistance to its mechanism of action, often while maintaining HER2 expression and signaling dependence. Thus, “next-generation” biologics targeting HER2 but providing novel effector mechanisms of action may provide avenues to combat resistance. The ability to encode unnatural amino acids allows unique site-specific drug conjugates as well as multispecific molecules to be made and developed against HER2-dependent tumors. This broad-based technology could potentially be applied to any antibody therapeutic target.