title: A novel bispecific antibody, S-Fab, induces potent cancer cell killing.
abstract: Bispecific antibodies that engage immune cells to kill cancer cells have been actively studied in cancer immunotherapy. In this study, we present a novel bispecific format, S-Fab, fabricated by linking a single-domain anti-carcinoembryonic antigen VHH to a conventional anti-CD3 Fab. In contrast to most bispecific antibodies, the S-Fab bispecific antibody can be efficiently expressed and purified from bacteria. The purified S-Fab is stable in serum and is able to recruit T cells to drive potent cancer cell killing. In xenograft models, the S-Fab antibody suppresses tumor growth in the presence of human immune cells. Our study suggested that the bispecific S-Fab format can be applied to a wide range of immunotherapies.
authors.affiliation: *School of Pharmaceutical Sciences †Centre for Cellular & Structural biology, Sun Yat-Sen University, Guangzhou ‡Peking University Cancer Hospital, Beijing Institute for Cancer Research §General Staff Department of PLA, Health Division of Guard Bureau, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Ping
authors.initials: P
authors.lastname: He
authors.forename: Changhua
authors.initials: C
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.forename: Siqi
authors.initials: S
authors.lastname: Chen
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Yawei
authors.initials: Y
authors.lastname: Liu
authors.forename: Ji
authors.initials: J
authors.lastname: Miao
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology* / Q000627:therapeutic use; D017252:CD3 Complex / Q000276:immunology*; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology* / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D016688:Mice, Inbred NOD; D023041:Xenograft Model Antitumor Assays
chemical_list: D018033:Antibodies, Bispecific; D017252:CD3 Complex; D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments