title: Pentamerisation of a scFv directed against TRAIL receptor 2 increases its antitumour efficacy.
abstract: Single-chain variable fragments (scFvs) have been considered as promising therapeutic drugs. However, their low affinity and rapid clearance from the blood have limited their wider application clinically. In this study, we aimed to improve scFv antibodies by multimerising a scFv against the death receptor 5 (DR5, TNFR10B) through fusion with a coiled-coil domain of human cartilage oligomeric matrix protein 48. By forming a pentamer, nick-named a combody, the avidity of the scFv increased 10⁴-fold and combody was more effective than its monomeric counterpart for antitumour activity in both in vitro and in vivo experiments.
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology-CASPMI, Institute of Microbiology, Chinese Academy of Sciences, Beijing, PRC.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: He
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000235:genetics; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000628:therapy; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058105:Polymerization; D015202:Protein Engineering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors* / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D057127:Single-Chain Antibodies / Q000008:administration & dosage / Q000737:chemistry* / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D011993:Recombinant Fusion Proteins; D057127:Single-Chain Antibodies