EDB and VEGF bispecific aptide fusion proteins for potential anti-angiogenic therapy = 혈관생성억제를 위한 EDB와 VEGF에 이중특이적인 앱타이드 융합단백질

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Angiogenesis plays an essential role in tumor growth and metastasis. Anti-angiogenic therapy has been considered effective approach to war various cancers. Although many antiangiongenic agents, especially vascular endothelial growth factor (VEGF) inhibitors, showed promising results in animal models, the efficacy in cancer patients was more modest in terms of overall survival and some vascular-related toxicities often hindered the long-term treatment. Thus, more potent and safe strategy is needed. A number of antibodies and recombinant affinity molecules are explored to find their potential therapeutic value. Our group recently developed a peptide scaffold termed ‘aptide’ that has high affinity and selectivity onto its target. Here, I describe a design and preparation of EDB and VEGF bisepcific aptide fusion proteins for potential anti-angiogenic therapy. In chapter 2, in order to achieve more efficient therapy, I modified VEGF-trap, which is currently used in the clinic, by fusing tumor targeting ligand, an aptide targeting EDB ($APT_{EDB}$). Resulting recombinant protein, VEGF-Trap-$APT_{EDB}$ was secreted from mammalian cell, purified, and showed dual-binding activities. In addition, it showed anti-angiogenic effect and tumor-targeting ability in vitro. We expect VEGF-trap-$APT_{EDB}$ may provide more efficient and safe therapeutic value than VEGF-Trap. In chapter 3, I described a potential anti-angiogenic platform using two aptides. Given that our VEGF-targeting aptide ($APT_{VEGF}$) had anti-angiogenic effect in choroidal and retinal neovascularization in vivo, I designed so-called bispecific aptibody for cancer therapy, by fusing on $APT_{VEGF}$ one side of human Fc of IgG and $APT_{EDB}$ on the other side for tumor targeting. It was secreted from mammalian cell, purified and examined its target binding activities and dualbinding activity. Although present study failed to show dual-binding activity, this study may provide directions for designing bispecific aptide-fusion platforms for potential cancer therapy.
Advisors
Jon, Sangyongresearcher전상용researcher
Description
한국과학기술원 :생명과학과,
Publisher
한국과학기술원
Issue Date
2015
Identifier
325007
Language
eng
Description

학위논문(석사) - 한국과학기술원 : 생명과학과, 2015.2,[v, 64 p. :]

Keywords

bispecific▼aaptide▼aVEGF▼aEDB▼aangiogenesis; 이중특이적▼a앱타이드▼a신혈관생성

URI
http://hdl.handle.net/10203/266279
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=849295&flag=dissertation
Appears in Collection
BS-Theses_Master(석사논문)
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