dc.contributor.advisor | Gürsel, İhsan | |
dc.contributor.author | Kılgöz, Havva Özgen | |
dc.date.accessioned | 2018-08-31T13:11:30Z | |
dc.date.available | 2018-08-31T13:11:30Z | |
dc.date.copyright | 2018-08 | |
dc.date.issued | 2018-08 | |
dc.date.submitted | 2018-08-29 | |
dc.identifier.uri | http://hdl.handle.net/11693/47762 | |
dc.description | Cataloged from PDF version of article. | en_US |
dc.description | Thesis (M.S.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2018. | en_US |
dc.description | Includes bibliographical references (leaves 88-94). | en_US |
dc.description.abstract | Exosomes are type of extracellular vesicles secreted from almost all cell types and
carry numerous biological molecules such as nucleic acids, protein and lipids. They
mediate many cellular processes including cellular communication and immune
responses. Accumulating evidence suggests that these vesicles play a key role in the
pathogenesis of inflammatory diseases, infectious diseases and many malignancies.
The significant role of exosomes in cellular level also describe their intriguing
potential in cancer therapeutics.
The primary aim of this thesis is to identify the immunomodulatory roles of distinct
exosome species and extend the knowledge of exosome utilization in immunotherapy.
The exosomes purified from i) RAW264.7 (murine macrophage-like), ii) EG7 (murine
T cell lymphoma), and iii) HUH7 (human hepatocellular carcinoma) had distinct
characteristics as well as immunomodulatory features upon murine splenocyte
stimulation either alone or in combination with poly(I:C) (a TLR3 ligand), R848(a
TLR7/8 ligand), and CpG ODN(a TLR9 ligand). Strikingly, these cell line-derived
exosomes displayed changing internalization kinetics by immune cells.
Furthermore, the involvement of exosomes in the liver disease progression in the
course of Hepatitis B virus (HBV) infection, cirrhosis and hepatocellular carcinoma
(HCC) was investigated. As a result of patients’ exosome stimulation assays with
healthy peripheral blood mononuclear cells (PBMCs) and murine splenocytes, patient
plasma-derived exosomes had inflammatory effects correlated with the severity of
liver damage suggesting that these exosomes might have a pathological role in liver
disease progression and/or pathogenesis. In the final part, we used a dehydration-rehydration technique enabling external
loading of desired Toll-like receptors (TLR) ligand within exosome and liposome. We
developed a robust therapeutic vaccine delivery system in which injection of
therapeutic vaccine to tumor burden animals enhanced anti-tumor activity and
prolonged survival of HCC xenografts. In summary, this approach could broaden the
immunotherapeutic utility of exosomes in the clinic. | en_US |
dc.description.statementofresponsibility | by Havva Özgen Kılgöz. | en_US |
dc.format.extent | xx, 108 leaves : illustrations (some color), charts (some color) ; 30 cm. | en_US |
dc.language.iso | English | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Exosomes | en_US |
dc.subject | TLRs | en_US |
dc.subject | HBV Infection | en_US |
dc.subject | Cirrhosis | en_US |
dc.subject | HCC | en_US |
dc.subject | Nanocarrier | en_US |
dc.subject | Immunotherapy | en_US |
dc.title | Immunomodulatory effects of exosomes: promising candidates in immunotherapy | en_US |
dc.title.alternative | Eksozomların immünomodülator etkileri: immün tedavide umut verici adaylar | en_US |
dc.type | Thesis | en_US |
dc.department | Department of Molecular Biology and Genetics | en_US |
dc.publisher | Bilkent University | en_US |
dc.description.degree | M.S. | en_US |
dc.identifier.itemid | B158924 | |
dc.embargo.release | 2021-08-16 | |