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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article numbere1524694
JournalOncoImmunology
Volume8
Issue number1
DOIs
StatePublished - Jan 2 2019

Fingerprint

Epitopes
Vaccination
Neoplasms
varespladib methyl
Therapeutics
HLA-A2 Antigen
Vaccines
HLA-DR1 Antigen
Stearic Acids
Uterine Cervical Neoplasms
Immunotherapy
Mass Spectrometry
Survival

Keywords

  • A2.DR1
  • Cancer immunotherapy
  • HLA-humanized mouse model
  • PAP-A2
  • human papillomavirus (HPV)
  • therapeutic vaccination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

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

In: OncoImmunology, Vol. 8, No. 1, e1524694, 02.01.2019.

Research output: Contribution to journalArticle

Kruse, S, Büchler, M, Uhl, P, Sauter, M, Scherer, P, Lan, TCT, Zottnick, S, Klevenz, A, Yang, R, Rösl, F, Mier, W & Riemer, AB 2019, 'Therapeutic vaccination using minimal HPV16 epitopes in a novel MHC-humanized murine HPV tumor model', OncoImmunology, vol. 8, no. 1, e1524694. https://doi.org/10.1080/2162402X.2018.1524694
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. / Therapeutic vaccination using minimal HPV16 epitopes in a novel MHC-humanized murine HPV tumor model. In: OncoImmunology. 2019 ; Vol. 8, No. 1.
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