title: Testing the anti-fibrotic potential of the single-chain Fv antibody against the α2 C-terminal telopeptide of collagen I.
abstract: Abstract This study focuses on the single-chain fragment variable (scFv) variant of the original IgA-type antibody, recognizing the α2 C-terminal telopeptide (α2Ct) of human collagen I, designed to inhibit post-traumatic localized fibrosis via blocking the formation of collagen-rich deposits. We have demonstrated that the scFv construct expressed in yeast cells was able to fold into an immunoglobulin-like conformation, but it was prone to forming soluble aggregates. Functional assays, however, indicate that the scFv construct specifically binds to the α2Ct epitope and inhibits collagen fibril formation both in vitro and in a cell culture model representing tissues that undergo post-traumatic fibrosis. Thus, the presented study demonstrates the potential of the scFv variant to serve as an inhibitor of the excessive formation of collagen-rich fibrotic deposits, and it reveals certain limitations associated with the current stage of development of this antibody construct.
authors.affiliation: Department of Orthopaedic Surgery, Jefferson Medical College, Thomas Jefferson University , Philadelphia, PA , USA and.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Fertala
authors.forename: James
authors.initials: J
authors.lastname: Kostas
authors.forename: Cheryl
authors.initials: C
authors.lastname: Hou
authors.forename: Andrzej
authors.initials: A
authors.lastname: Steplewski
authors.forename: Pedro
authors.initials: P
authors.lastname: Beredjiklian
authors.forename: Joseph
authors.initials: J
authors.lastname: Abboud
authors.forename: William V
authors.initials: WV
authors.lastname: Arnold
authors.forename: Gerald
authors.initials: G
authors.lastname: Williams
authors.forename: Andrzej
authors.initials: A
authors.lastname: Fertala
mesh_terms: D002460:Cell Line; D002921:Cicatrix / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D024042:Collagen Type I / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D000939:Epitopes / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D057127:Single-Chain Antibodies / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
chemical_list: D024042:Collagen Type I; D000939:Epitopes; D010455:Peptides; D057127:Single-Chain Antibodies; C052929:collagen type I trimeric cross-linked peptide