title: Single domain antibody-based bispecific antibody induces potent specific anti-tumor activity.
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.
authors.affiliation: a School of Pharmaceutical Sciences, Sun Yat-Sen University , Guangzhou , China.|b Center for Cellular & Structural Biology , Sun Yat-Sen University , Guangzhou , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: a School of Pharmaceutical Sciences, Sun Yat-Sen University , Guangzhou , China.|b Center for Cellular & Structural Biology , Sun Yat-Sen University , Guangzhou , China.
authors.forename: Changhua
authors.initials: C
authors.lastname: Zhou
authors.affiliation: a School of Pharmaceutical Sciences, Sun Yat-Sen University , Guangzhou , China.|b Center for Cellular & Structural Biology , Sun Yat-Sen University , Guangzhou , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.affiliation: a School of Pharmaceutical Sciences, Sun Yat-Sen University , Guangzhou , China.|b Center for Cellular & Structural Biology , Sun Yat-Sen University , Guangzhou , China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhong
authors.affiliation: a School of Pharmaceutical Sciences, Sun Yat-Sen University , Guangzhou , China.|b Center for Cellular & Structural Biology , Sun Yat-Sen University , Guangzhou , China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Chen
authors.affiliation: a School of Pharmaceutical Sciences, Sun Yat-Sen University , Guangzhou , China.|b Center for Cellular & Structural Biology , Sun Yat-Sen University , Guangzhou , China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: a School of Pharmaceutical Sciences, Sun Yat-Sen University , Guangzhou , China.|b Center for Cellular & Structural Biology , Sun Yat-Sen University , Guangzhou , China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015195:Drug Design; D019073:HT29 Cells; D006801:Humans; D000070557:Immunoglobulin Domains; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D017452:Receptors, IgG / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D018033:Antibodies, Bispecific; D002272:Carcinoembryonic Antigen; D017452:Receptors, IgG; D011994:Recombinant Proteins
keywords: Bispecific antibody; CD16; CEA; SS-Fc; single-domain antibody