title: Novel anti-EPHA2 antibody, DS-8895a for cancer treatment.
abstract: Overexpression of EPHA2 has been observed in multiple cancers and reported to be associated with poor prognosis. Here, we produced an afucosylated humanized anti-EPHA2 monoclonal antibody (mAb), DS-8895a for cancer treatment. The antibody recognizes the extracellular juxtamembrane region of EPHA2 and therefore can bind to both full-length and truncated forms of EPHA2, which are anchored to cell membranes and recently reported to be produced by post-translational cleavage in tumors. DS-8895a exhibited markedly increased antibody dependent cellular cytotoxicity (ADCC) in vitro and also inhibited tumor growth in EPHA2-positive human breast cancer MDA-MB-231 and human gastric cancer SNU-16 xenograft mouse models. Moreover, DS-8895a in combination with cisplatin (CDDP) showed better efficacy than each of the monotherapies did in the human gastric cancer model. These results suggest that a novel antibody, DS-8895a has therapeutic potential against EPHA2-expressing tumors.
authors.affiliation: a Biologics & Immuno-Oncology Laboratories , Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo , Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hasegawa
authors.affiliation: a Biologics & Immuno-Oncology Laboratories , Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo , Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sue
authors.affiliation: a Biologics & Immuno-Oncology Laboratories , Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo , Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Yamato
authors.affiliation: a Biologics & Immuno-Oncology Laboratories , Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo , Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Ichikawa
authors.affiliation: a Biologics & Immuno-Oncology Laboratories , Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo , Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Ishida
authors.affiliation: b Translational Medicine & Clinical Pharmacology Department , Daiichi Sankyo Co., Ltd., Shinagawa-ku , Tokyo , Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Shibutani
authors.affiliation: a Biologics & Immuno-Oncology Laboratories , Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo , Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kitamura
authors.affiliation: a Biologics & Immuno-Oncology Laboratories , Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo , Japan.
authors.forename: Teiji
authors.initials: T
authors.lastname: Wada
authors.affiliation: a Biologics & Immuno-Oncology Laboratories , Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo , Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Agatsuma
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D011897:Random Allocation; D036104:Receptor, EphA2 / Q000276:immunology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000276:immunology; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D036104:Receptor, EphA2; D002945:Cisplatin
keywords: Afucosylated antibody; DS-8895a; EPHA2; Monoclonal antibody (mAb); antibody-dependent cellular cytotoxicity (ADCC); cancer; natural killer (NK) cells