Single domain antibody-based bispecific antibody induces potent specific anti-tumor activity. Issue 12 (1st December 2016)

• Record Type: Journal Article
• Authors: Li, Jing; Zhou, Changhua; Dong, Bin; Zhong, Hong; Chen, Siqi; Li, Qing; Wang, Zhong
• Is Part Of: Cancer biology & therapy. Volume 17:Issue 12(2016)
• Page Start: 1231
• Page End: 1239
• Publication Date: 2016-12-01
• Subjects: Bispecific antibody -- CD16 -- CEA -- single-domain antibody -- SS-Fc; 616.99406
• DOI: 10.1080/15384047.2016.1235659
• Languages: English
• ISSNs: 1538-4047

Abstract

ABSTRACT: Bispecific antibodies have emerged as powerful therapeutic agents given their high specificity and ability to induce a potent immune response. Various bispecific antibody formats have been designed and studied regarding their applications in cancer therapy, though associated with issues of short half-life or manufacturing difficulties. Herein, a novel bispecific antibody, SS-Fc, was constructed by pairing 2 single-domain antibodies, anti-CD16 and anti-CEA, which were fused with CH3 "knobs into holes" mutations individually. SS-Fc was expressed and purified from E.coli. In vitro and in vivo experiments confirmed that SS-Fc can form a heterodimeric bispecific antibody when expressed and purified from E. coli . By engaging natural killer (NK) cells through an anti-CD16 single domain antibody, the SS-Fc bispecific antibody exhibited potent in vitro and in vivo cytotoxicity against cancer cells with carcinoembryonic antigen (CEA) expression. Thus, SS-Fc represents a novel bispecific antibody format that can be applied to a wide range of both discovery and clinical applications.