title: Superior in vivo efficacy of afucosylated trastuzumab in the treatment of HER2-amplified breast cancer.
abstract: The enhancement of immune effector functions has been proposed as a potential strategy for increasing the efficacy of therapeutic antibodies. Here, we show that removing fucose from trastuzumab (Herceptin) increased its binding to FcgammaRIIIa, enhanced antibody-dependent cell-mediated cytotoxicity, and more than doubled the median progression-free survival when compared with conventional trastuzumab in treating preclinical models of HER2-amplified breast cancer. Our results show that afucosylated trastuzumab has superior efficacy in treating in vivo models of HER2-amplified breast cancer and support the development of effector function-enhanced antibodies for solid tumor therapy.
authors.affiliation: Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: Teemu T
authors.initials: TT
authors.lastname: Junttila
authors.forename: Kathryn
authors.initials: K
authors.lastname: Parsons
authors.forename: Christine
authors.initials: C
authors.lastname: Olsson
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Lu
authors.forename: Yan
authors.initials: Y
authors.lastname: Xin
authors.forename: Julie
authors.initials: J
authors.lastname: Theriault
authors.forename: Lisa
authors.initials: L
authors.lastname: Crocker
authors.forename: Oliver
authors.initials: O
authors.lastname: Pabonan
authors.forename: Tomasz
authors.initials: T
authors.lastname: Baginski
authors.forename: Gloria
authors.initials: G
authors.lastname: Meng
authors.forename: Klara
authors.initials: K
authors.lastname: Totpal
authors.forename: Robert F
authors.initials: RF
authors.lastname: Kelley
authors.forename: Mark X
authors.initials: MX
authors.lastname: Sliwkowski
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005643:Fucose / Q000737:chemistry; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D005643:Fucose; D018719:Erb-b2 Receptor Tyrosine Kinases; D017452:Receptors, IgG; D000068878:Trastuzumab; C496124:FCGR3A protein, human