Therapeutic vaccination using minimal HPV16 epitopes in a novel MHC-humanized murine HPV tumor model
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 cance...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2019
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| In: |
OncoImmunology
Year: 2018, Volume: 8, Issue: 1 |
| ISSN: | 2162-402X |
| DOI: | 10.1080/2162402X.2018.1524694 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1080/2162402X.2018.1524694
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Published online: 29 October 2018 Gesehen am /05.06.2019 |
| Physical Description: | Online Resource |
| ISSN: | 2162-402X |
| DOI: | 10.1080/2162402X.2018.1524694 |