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

Autor:	Kruse S; Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany., Büchler M; Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany., Uhl P; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.; Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany., Sauter M; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.; Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany., Scherer P; Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, Germany., Lan TCT; Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, Germany., Zottnick S; Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany., Klevenz A; Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, Germany., Yang R; Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.; Viral Transformation Mechanisms, German Cancer Research Center (DKFZ), Heidelberg, Germany., Rösl F; Viral Transformation Mechanisms, German Cancer Research Center (DKFZ), Heidelberg, Germany., Mier W; Department of Nuclear Medicine, Heidelberg University Hospital, Heidelberg, Germany., Riemer AB; Immunotherapy & Immunoprevention, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Molecular Vaccine Design, German Center for Infection Research (DZIF), Partner Site Heidelberg, Heidelberg, Germany.
Jazyk:	angličtina
Zdroj:	Oncoimmunology [Oncoimmunology] 2018 Oct 29; Vol. 8 (1), pp. e1524694. Date of Electronic Publication: 2018 Oct 29 (Print Publication: 2019).
DOI:	10.1080/2162402X.2018.1524694
Abstrakt:	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:	MEDLINE
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