In face of the necessity of broadly acting and highly effective vaccines capable of eliminating/preventing human cancers with insufficient mutated antigens, we introduced the concept of Virus-Like Vaccines (VLVs). This strategy combines a replication-deficient retrovirus encoding virus structural proteins. These proteins assemble into secreted virus-like particles (VLPs) that deliver the target antigen to the immune system rising both humoral and cellular immune responses. Here, we use an adenoviral vector encoding the group specific antigen (Gag) and the glycoprotein of the viral envelope (Env) from endogenous retrovirus (ERV). Since ERV Env is reported to have immunosuppressive properties that support tumor establishment and development, we designed a modified vaccine that includes a mutation on the Env immunosuppressive domain (ISD) that prevents the vaccine from being immunosuppressive itself. In our studies, we demonstrate that VLVs are able to induce strong, broad, and long-lasting ERV Env specific CD8+ T cell by flow cytometry and antibody responses by ELISA in mice. Furthermore, the modified vaccine is of special interest to future research as it proved to significantly delay mouse tumor growth in a therapeutic setup. Nevertheless, we now need to address the principal host related developmental uncertainties in translating our achievements into the clinical setting. This goal can be accomplished by raising human T cells capable of targeting human cancers ex vivo. Furthermore, to support the translation of our work, we tested the ability to rise adaptive responses upon vaccination in non-human primates (NHP) which endogenously express ERVs similar to humans (in collaboration with IPB University, Indonesia). Fellowship granted by Innovation Fund Denmark.
Disclosure Information J. Daradoumis: A. Employment (full or part-time); Significant; InProTher Aps. B. Research Grant (principal investigator, collaborator or consultant and pending grants as well as grants already received); Significant; Innovation Fund Denmark. P.J. Holst: A. Employment (full or part-time); Significant; InProTher Aps. E. Ownership Interest (stock, stock options, patent or other intellectual property); Significant; InProTher. K.N. Nielsen: A. Employment (full or part-time); Significant; InProTher Aps.
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