Novel anti-EPHA2 antibody, DS-8895a for cancer treatment. Issue 11 (1st November 2016)

• Record Type: Journal Article
• Authors: Hasegawa, Jun; Sue, Mayumi; Yamato, Michiko; Ichikawa, Junya; Ishida, Saori; Shibutani, Tomoko; Kitamura, Michiko; Wada, Teiji; Agatsuma, Toshinori
• Is Part Of: Cancer biology & therapy. Volume 17:Issue 11(2016)
• Page Start: 1158
• Page End: 1167
• Publication Date: 2016-11-01
• Subjects: Afucosylated antibody -- antibody-dependent cellular cytotoxicity (ADCC) -- cancer -- DS-8895a -- EPHA2 -- Monoclonal antibody (mAb) -- natural killer (NK) cells; 616.99406
• DOI: 10.1080/15384047.2016.1235663
• Languages: English
• ISSNs: 1538-4047

Abstract

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.