title: Antibody conjugates with unnatural amino acids.
abstract: Antibody conjugates are important in many areas of medicine and biological research, and antibody-drug conjugates (ADCs) are becoming an important next generation class of therapeutics for cancer treatment. Early conjugation technologies relied upon random conjugation to multiple amino acid side chains, resulting in heterogeneous mixtures of labeled antibody. Recent studies, however, strongly support the notion that site-specific conjugation produces a homogeneous population of antibody conjugates with improved pharmacologic properties over randomly coupled molecules. Genetically incorporated unnatural amino acids (uAAs) allow unique orthogonal coupling strategies compared to those used for the 20 naturally occurring amino acids. Thus, uAAs provide a novel paradigm for creation of next generation ADCs. Additionally, uAA-based site-specific conjugation could also empower creation of additional multifunctional conjugates important as biopharmaceuticals, diagnostics, or reagents.
authors.affiliation: †Sutro Biopharma, 310 Utah Avenue, Suite 150, South San Francisco, California 94080, United States.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Hallam
authors.affiliation: ‡The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Erik
authors.initials: E
authors.lastname: Wold
authors.affiliation: §Ambrx, Inc. 10975 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Alan
authors.initials: A
authors.lastname: Wahl
authors.affiliation: ‡The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Vaughn V
authors.initials: VV
authors.lastname: Smider
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D000596:Amino Acids; D000906:Antibodies; D018796:Immunoconjugates
keywords: Chinese hamster ovary; antibody−drug conjugate; drug:antibody ratio; heavy chain; light chain; pharmacokinetics; tRNA synthetase; unnatural amino acid