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

通过在受感染细胞或病毒样颗粒上呈递选定的肿瘤相关抗原,实现抗原特异性溶瘤 MV 肿瘤疫苗

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作者:Stefan Hutzler, Stephanie Erbar, Robert A Jabulowsky, Jan R H Hanauer, Jürgen H Schnotz, Tim Beissert, Bianca S Bodmer, Regina Eberle, Klaus Boller, Thorsten Klamp, Ugur Sahin, Michael D Mühlebach

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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