Therapeutic vaccination using minimal HPV16 epitopes in a novel MHC-humanized murine HPV tumor model
| Autor: | Philipp Scherer, Marleen Büchler, Samantha Zottnick, Max Sauter, Walter Mier, Sebastian Kruse, Tammy C.T. Lan, Frank Rösl, Ruwen Yang, Angelika B. Riemer, Philipp Uhl, Alexandra Klevenz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
lcsh:Immunologic diseases. Allergy medicine.medical_treatment Immunology chemical and pharmacologic phenomena Major histocompatibility complex lcsh:RC254-282 Epitope 03 medical and health sciences 0302 clinical medicine Cancer immunotherapy Immunology and Allergy Medicine a2.dr1 human papillomavirus (hpv) Original Research hla-humanized mouse model Ideal (set theory) cancer immunotherapy biology business.industry therapeutic vaccination virus diseases Treatment options pap-a2 Immunotherapy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens female genital diseases and pregnancy complications Vaccination 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein business lcsh:RC581-607 |
| Zdroj: | OncoImmunology, Vol 8, Iss 1 (2019) |
| ISSN: | 2162-4011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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