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Comparative study of different vaccine platforms for therapeutic vaccination in cancer

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  1. Tez No: 852469
  2. Yazar: YUSUF EMRE ERTEM
  3. Danışmanlar: DR. SONJA (S.I) BUSCHOW
  4. Tez Türü: Yüksek Lisans
  5. Konular: Gastroenteroloji, Gastroenterology
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2022
  8. Dil: İngilizce
  9. Üniversite: Erasmus Universiteit Rotterdam
  10. Enstitü: Yurtdışı Enstitü
  11. Ana Bilim Dalı: Belirtilmemiş.
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: 54

Özet

Antigen presentation is one of the cornerstones of our immune system. It is often discussed in terms of fighting against infectious diseases. However, its role in cancer should not be overlooked. The current thought is that tumor cells can be seen as“non-self”since they express antigens that are not seen in healthy cells. However, hurdles created by the tumor cells, such as alterations in antigen presentation, lead to immune evasion of cancer. Therapeutic cancer vaccines aim to feed selected antigens to dendritic cells (DCs) to activate cellular immunity against that particular Tumor Associated Antigen (TAA), which is produced by the tumor cells, and then allow the elimination of the target cells, expressing that antigen. Potential platforms to be used for therapeutic vaccination include, amongst others: whole tumor lysate (WTL)-based vaccines, synthetic long peptides (SLPs)-based vaccines, and mRNA-based vaccines. Until now, it has been unclear which of these vaccine platforms yields the best anti-tumor response. In this study, we used genetically engineered HAP1 cell lines in order to test the aforementioned WTL efficiency in terms of the resulting vaccine antigen immunopeptidome to mimic the peptide repertoire on DCs. To identify Survivin, as a prototype TAA, immunopeptidome in the endogenous model, mass spectrometry-based approach was applied to the model cell line HAP1 which the HLA gene is knocked out, but HLA-A2 and Survivin gene is inserted. To test WTL vaccination, HAP1 cells without any HLA but overexpressing Survivin, were cultured, lysed, and fed to monocyte-derived dendritic cells (moDCs). This approach allowed us to compare antigen presentation and resulting immunopeptidome of the tumor situation to that antigen-fed moDC-based repertoire. However, the exogenous immune repertoire has yet to be obtained. This study, for now, served as a potential pipeline to study different vaccine platforms in terms of their immunopeptidomics in the future. KEYWORDS: Therapeutic vaccination, whole tumor lysate, moDC, HAP1, immunopeptidomics, Survivin, antigen presentation

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