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Phage Display Selection of Antibody Fragments targeted to VEGFR-3 Dimerization Domain

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dc.date.accessioned 2014-10-07T12:00:14Z
dc.date.accessioned 2015-07-29T08:27:16Z
dc.date.available 2014-10-07T12:00:14Z
dc.date.available 2015-07-29T08:27:16Z
dc.date.issued 2014-10-07
dc.identifier.uri http://hdl.handle.net/10138/136105
dc.title Phage Display Selection of Antibody Fragments targeted to VEGFR-3 Dimerization Domain en
ethesis.discipline Muu fi
ethesis.department Haartman institutet sv
ethesis.department Haartman Institute en
ethesis.department Kliinisteoreettinen laitos fi
ethesis.faculty Faculty of Medicine en
ethesis.faculty Medicinska fakulteten sv
ethesis.faculty Lääketieteellinen tiedekunta fi
ethesis.faculty.URI http://data.hulib.helsinki.fi/id/a4d5aaa2-b5aa-41a7-ba4c-e5e0df7a902d
ethesis.university.URI http://data.hulib.helsinki.fi/id/50ae46d8-7ba9-4821-877c-c994c78b0d97
ethesis.university Helsingfors universitet sv
ethesis.university University of Helsinki en
ethesis.university Helsingin yliopisto fi
dct.creator Lee, Yoke Seng
dct.issued 2014
dct.language.ISO639-2 eng
dct.abstract The inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) signaling has important implications in circumventing tumor angiogenesis and lymphangiogenesis. Monoclonal antibodies inhibiting ligand binding to its receptor are already in clinical trials, and a murine antibody targeted towards the dimerization domain of the receptor has recently been described. This paves the way for new targeting modalities for counteracting receptor dimerization and activation, but human antibodies have thus far not been reported. We sought to generate novel human Fab antibody fragments targeted towards the dimerization domain of VEGFR-3, by surveying the artificial human Fab phage display library (size ~ 3 x 10^10) through affinity selections with the antigens b-R3D45 (biotinylated domains 4 and 5 of VEGFR-3) and R3D17 (full length extracellular domain of VEGFR-3) in mobile and solid phase panning respectively. After 4 to 5 rounds of affinity selection, significant enrichment of VEGFR-3-specific clones was achieved, and subsequent characterization revealed at least 11 promising novel human Fab candidates. These Fabs were expressed in bacterial expression systems and validated by immunoblotting. Future work may be directed towards their purification and assessment in functional assays, such as the inhibition of ligand-mediated cell survival. In conclusion, this study has demonstrated the robustness of the antibody library in generating novel human Fabs against the VEGFR-3 dimerization interface that could be translated towards the clinical inhibition of pathological angiogenesis and lymphangiogenesis in tumors. en
dct.language en
ethesis.language.URI http://data.hulib.helsinki.fi/id/languages/eng
ethesis.language English en
ethesis.language englanti fi
ethesis.language engelska sv
ethesis.supervisor Saksela, Kalle
ethesis.thesistype pro gradu-avhandlingar sv
ethesis.thesistype pro gradu -tutkielmat fi
ethesis.thesistype master's thesis en
ethesis.thesistype.URI http://data.hulib.helsinki.fi/id/thesistypes/mastersthesis
dct.identifier.urn URN:NBN:fi:hulib-201507282524
dc.type.dcmitype Text
ethesis-internal.updated TRUE2

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