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Sci Rep. 2017 Dec 4;7(1):16892. doi: 10.1038/s41598-017-16928-8.

Antigen-specific oncolytic MV-based tumor vaccines through presentation of selected tumor-associated antigens on infected cells or virus-like particles.

Author information

1
Section Product Testing of IVMPs, Division of Veterinary Medicine, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, D-63225, Langen, Germany.
2
Biopharmaceutical New Technologies (BioNTech) Corporation, An der Goldgrube 12, D-55131, Mainz, Germany.
3
TRON - Translational Oncology at the University Medical Center of the Johannes Gutenberg University gGmbH, Freiligrathstr. 12, D-55131, Mainz, Germany.
4
Section Morphology, Division of Immunology, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, D-63225, Langen, Germany.
5
Section Product Testing of IVMPs, Division of Veterinary Medicine, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, D-63225, Langen, Germany. Michael.Muehlebach@pei.de.

Abstract

Recombinant vaccine strain-derived measles virus (MV) is clinically tested both as vaccine platform to protect against other pathogens and as oncolytic virus for tumor treatment. To investigate the potential synergism in anti-tumoral efficacy of oncolytic and vaccine properties, we chose Ovalbumin and an ideal tumor antigen, claudin-6, for pre-clinical proof of concept. To enhance immunogenicity, both antigens were presented by retroviral virus-like particle produced in situ during MV-infection. All recombinant MV revealed normal growths, genetic stability, and proper expression and presentation of both antigens. Potent antigen-specific humoral and cellular immunity were found in immunized MV-susceptible IFNAR-/--CD46Ge mice. These immune responses significantly inhibited metastasis formation or increased therapeutic efficacy compared to control MV in respective novel in vivo tumor models using syngeneic B16-hCD46/mCLDN6 murine melanoma cells. These data indicate the potential of MV to trigger selected tumor antigen-specific immune responses on top of direct tumor lysis for enhanced efficacy.

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