title: Antibody drug conjugates.
abstract: Antibody drug conjugates (ADCs) have emerged as a viable option in targeted delivery of highly potent cytotoxic drugs in treatment of solid tumors. At the time of writing, only two ADCs have received regulatory approval with >40 others in clinical development. The first generation ADCs suffered from a lack of specificity in amino acid site-conjugations, yielding statistically heterogeneous stoichiometric ratios of drug molecules per antibody molecule. For the second generation ADCs, however, site-specific amino acid conjugation using enzymatic ligation, introduction of unnatural amino acids, and site-specific protein engineering hold promise to alleviate some of the current technical limitations. The rapid progress in technology platforms and antibody engineering has introduced novel linkers, site-specific conjugation chemistry, and new payload candidates that could possibly be exploited in the context of ADCs. A search using the Clinical Trial Database registry ( www.clinicaltrials.gov ), using the keyword 'antibody drug conjugate', yielded ~270 hits. The main focus of this article is to present a brief overview of the recent developments and current challenges related to ADC development.
authors.affiliation: Teva Branded Pharmaceutical Products R & D Inc, West Chester, PA, 19380, USA. rbakhtiar@msn.com.
authors.forename: Ray
authors.initials: R
authors.lastname: Bakhtiar
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D001666:Binding Sites, Antibody; D002986:Clinical Trials as Topic; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D015202:Protein Engineering
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates
keywords: Brentuximab vedotin; Chemical linkers; Conjugation; Cytotoxicity; Payload; Solid tumors; Transtuzumab emtansine