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

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 a...

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Bibliographic Details
Published in:	Scientific reports Vol. 7; no. 1; pp. 16892 - 15
Main Authors:	Hutzler, Stefan, Erbar, Stephanie, Jabulowsky, Robert A., Hanauer, Jan R. H., Schnotz, Jürgen H., Beissert, Tim, Bodmer, Bianca S., Eberle, Regina, Boller, Klaus, Klamp, Thorsten, Sahin, Ugur, Mühlebach, Michael D.
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 04-12-2017 Nature Publishing Group
Subjects:	13/44 631/326/596/2561 631/67/1059/2325 692/4017 Animal models Animals Antigen (tumor-associated) Antigen Presentation Antigens Antigens, Neoplasm - genetics Antigens, Neoplasm - immunology Antigens, Neoplasm - metabolism Autoantibodies - blood Autoantibodies - metabolism Cancer vaccines Cancer Vaccines - genetics Cancer Vaccines - immunology Cancer Vaccines - therapeutic use Cell Line, Tumor Cell-mediated immunity Cercopithecus aethiops Claudins - genetics Claudins - immunology Claudins - metabolism Humanities and Social Sciences Humoral immunity Immune response Immunity, Cellular Immunity, Humoral Immunization Immunogenicity Interferon-gamma - metabolism Lung Neoplasms - secondary Lung Neoplasms - therapy Lysis Measles virus - genetics Melanoma Melanoma, Experimental - immunology Melanoma, Experimental - therapy Metastases Mice Mice, Transgenic multidisciplinary Oncolysis Oncolytic Virotherapy Ovalbumin Ovalbumin - genetics Ovalbumin - immunology Science Science (multidisciplinary) Synergism T cell receptors Tumors Vaccines Vaccines, Virus-Like Particle - genetics Vaccines, Virus-Like Particle - immunology Vaccines, Virus-Like Particle - therapeutic use Vero Cells Virus-like particles
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-017-16928-8