title: A novel single-chain antibody redirects adenovirus to IL13Rα2-expressing brain tumors.
abstract: The generation of a targeting agent that strictly binds to IL13Rα2 will significantly expand the therapeutic potential for the treatment of IL13Rα2-expressing cancers. In order to fulfill this goal, we generated a single-chain antibody (scFv47) from our parental IL13Rα2 monoclonal antibody and tested its binding properties. Furthermore, to demonstrate the potential therapeutic applicability of scFv47, we engineered an adenovirus by incorporating scFv47 as the targeting moiety in the viral fiber and characterized its properties in vitro and in vivo. The scFv47 binds to human recombinant IL13Rα2, but not to IL13Rα1 with a high affinity of 0.9 · 10(-9) M, similar to that of the parental antibody. Moreover, the scFv47 successfully redirects adenovirus to IL13Rα2 expressing glioma cells both in vitro and in vivo. Our data validate scFv47 as a highly selective IL13Rα2 targeting agent and justify further development of scFv47-modified oncolytic adenovirus and other therapeutics for the treatment of IL13Rα2-expressing glioma and other malignancies.
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Julius W
authors.initials: JW
authors.lastname: Kim
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jacob S
authors.initials: JS
authors.lastname: Young
authors.affiliation: Biophysics Core Facility, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Solomaha
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kanojia
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Maciej S
authors.initials: MS
authors.lastname: Lesniak
authors.affiliation: The Brain Tumor Center, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Irina V
authors.initials: IV
authors.lastname: Balyasnikova
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive / Q000276:immunology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005910:Glioma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000276:immunology / Q000378:metabolism; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008819:Mice, Nude; D018613:Microscopy, Confocal; D011485:Protein Binding / Q000276:immunology; D057127:Single-Chain Antibodies / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D020349:Surface Plasmon Resonance; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C508181:IL13RA1 protein, human; D053661:Interleukin-13 Receptor alpha1 Subunit; D053663:Interleukin-13 Receptor alpha2 Subunit; D057127:Single-Chain Antibodies; D049452:Green Fluorescent Proteins