title: New developments for antibody-drug conjugate-based therapeutic approaches.
abstract: The clinical success of Adcetris(®) (brentuximab vedotin) and Kadcyla(®) (ado-trastuzumab emtansine) has sparked clinical development of novel ADCs. These powerful anti-cancer agents are designed to allow specific targeting of highly potent cytotoxic agents to tumor cells while sparing healthy tissues. Despite the use of tumor-specific antibodies, the emerging clinical data with ADCs indicates that adverse effects frequently occur before ADCs have reached their optimal therapeutic dose, resulting in a relatively narrow therapeutic window. This review summarizes the therapeutic window of ADCs currently in clinical development, along with some strategies that may help to widen the window.
authors.affiliation: Genmab, Yalelaan 60, 3584 CM Utrecht, The Netherlands. Electronic address: b.degoeij@genmab.com.
authors.forename: Bart Ecg
authors.initials: BE
authors.lastname: de Goeij
authors.affiliation: ImmunoGen, Inc., 830 Winter Street, Waltham, MA 02451, United States.
authors.forename: John M
authors.initials: JM
authors.lastname: Lambert
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000079963:Brentuximab Vedotin; D002985:Clinical Protocols; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods* / Q000639:trends; D000922:Immunotoxins / Q000627:therapeutic use*; D008453:Maytansine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D018570:Risk Assessment; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018796:Immunoconjugates; D000922:Immunotoxins; D008453:Maytansine; D000079963:Brentuximab Vedotin; D000068878:Trastuzumab; D000080044:Ado-Trastuzumab Emtansine