A novel immuno-oncolytic virus-based dendritic cell therapeutic cancer vaccine

ended

Following decades of development, therapeutic cancer vaccines are beginning to gain momentum in demonstrating therapeutic effects, and they represent a particularly promising approach. The aim of therapeutic cancer vaccines is to stimulate immunity against tumor antigens, usually through the use of whole cells, peptides, or nucleic acids (i.e. mRNAs). Dendritic cell- (DC) based vaccines represent particularly interesting candidates for therapeutic cancer vaccine products due to their ability to cross-present antigens to T cells, thereby driving adaptive immune responses through induction of antigen-specific cytotoxic T lymphocytes. Despite the potential of DC-based cancer vaccines, several major limitations have hindered their success in clinical studies. These limitations include insufficient ex vivo maturation of DCs and challenges in selecting optimal tumor antigens to target. The aim of DCanVAX is to develop a novel oncolytic virus-based dendritic cell vaccine approach for systemic therapy of solid cancers. We propose that the use of a highly immuno-oncolytic virus as a mechanism to lyse tumor cells ex-vivo, will lead to the release of the entire tumor antigen library, as well as a cocktail of danger signals in response to the virus infection. By applying this highly immunogenic lysate to autologous DCs, an optimized and personalized DC vaccine can be generated. This method overcomes the major challenges that have been encountered by DC vaccine approaches in the clinic, by providing a potent mechanism of DC maturation and activation, while simultaneously exposing the DCs to the complete repertoire of tumor antigens that are specific to the patient, leading to potent and broad tumor-specific immune responses against the cancer. This approach can be developed for multiple solid cancer indications and combined with other immunotherapy approaches for potentially synergistic therapeutic effects.