Therapeutic vaccination using minimal HPV16 epitopes in a novel MHC-humanized murine HPV tumor model. (2nd January 2019)

• Record Type: Journal Article
• Authors: Kruse, Sebastian; Büchler, Marleen; Uhl, Philipp; Sauter, Max; Scherer, Philipp; Lan, Tammy C.T.; Zottnick, Samantha; Klevenz, Alexandra; Yang, Ruwen; Rösl, Frank; Mier, Walter; Riemer, Angelika B.
• Is Part Of: Oncoimmunology. Volume 8:Number 1(2019)
• Publication Date: 2019-01-02
• Subjects: Cancer immunotherapy -- therapeutic vaccination -- HLA-humanized mouse model -- human papillomavirus (HPV) -- A2.DR1 -- PAP-A2; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2018.1524694
• Languages: English
• ISSNs: 2162-402X

Abstract

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.