Therapeutic vaccination using minimal HPV16 epitopes in a novel MHC-humanized murine HPV tumor model

• Verfasst von: Kruse, Sebastian [VerfasserIn]
• Verfasst von: Büchler-Schäff, Marleen [VerfasserIn]
• Verfasst von: Uhl, Philipp [VerfasserIn]
• Verfasst von: Sauter, Max [VerfasserIn]
• Verfasst von: Yang, Ruwen [VerfasserIn]
• Verfasst von: Mier, Walter [VerfasserIn]
• Titel: Therapeutic vaccination using minimal HPV16 epitopes in a novel MHC-humanized murine HPV tumor model
• Verf.angabe: Sebastian Kruse, Marleen Büchler, Philipp Uhl, Max Sauter, Philipp Scherer, Tammy C.T. Lan, Samantha Zottnick, Alexandra Klevenz, Ruwen Yang, Frank Rösl, Walter Mier & Angelika B. Riemer
• Jahr: 2019
• Jahr des Originals: 2018
• Teil: volume:8
• Teil: year:2019
• Teil: number:1
• Fussnoten: Published online: 29 October 2018 ; Gesehen am /05.06.2019
• Titel Quelle: Enthalten in: OncoImmunology
• Ort Quelle: Abingdon : Taylor & Franics, 2012
• Jahr Quelle: 2019
• Band/Heft Quelle: 8(2019,1) Artikel-Nummer e1524694, ? Seiten
• ISSN Quelle: 2162-402X
• DOI: doi:10.1080/2162402X.2018.1524694
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: A2.DR1
• Sach-SW: Cancer immunotherapy
• Sach-SW: HLA-humanized mouse model
• Sach-SW: human papillomavirus (HPV)
• Sach-SW: PAP-A2
• Sach-SW: therapeutic vaccination
• K10plus-PPN: 1666836508

Abstract

Therapeutic vaccination as a treatment option for HPV-induced cancers is actively pursued because the two HPV proteins E6 and E7 represent ideal targets for immunotherapy, as they are non-self and expressed in all tumor stages. MHC-humanized mice are valuable tools for the study of therapeutic cancer vaccines - given the availability of a suitable tumor model. Here, we present for the first time an HPV16 tumor model suitable for fully MHC-humanized A2.DR1 mice, PAP-A2 cells, which in contrast to existing HPV16 tumor models allows the exclusive study of HLA-A2- and DR1-mediated immune responses, without any interfering murine MHC-presented epitopes. We used several HPV16 epitopes that were shown to be presented on human cervical cancer cells by mass spectrometry for therapeutic anti-tumor vaccination in the new tumor model. All epitopes were immunogenic when rendered amphiphilic by incorporation into a molecule containing stearic acids. Prophylactic and therapeutic vaccination experiments with the epitope E7/11-19 demonstrated that effective immune responses could be induced with these vaccination approaches in A2.DR1 mice. Interestingly, the combination of E7/11-19 with other immunogenic HPV16 E6/E7 epitopes caused a reduction of vaccine efficacy, although all tested combinations resulted in a survival benefit. In summary, we present the first HPV16 tumor model for exclusive studies of HLA-A2-mediated anti-HPV tumor immune responses and show anti-tumor efficacy of minimal epitope vaccines.