Oncolytic viruses as anticancer vaccines

Abstract

Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity, which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy.

Keywords: antitumor immune response; antitumor immunity; oncolytic agents; oncolytic virotherapy; oncolytic virus.

Figure 1

The figure illustrates the improved T cell priming in oncolytic virotherapy. Viral oncolysis of tumor cell induces immunogenic cell death by accumulation of PAMPs and accompanied by release of DAMPs. PAMPs and DAMPs activate antigen-presenting dendritic cells that can induce cytotoxic T cell responses against tumor-associated antigens or neoepitopes, respectively.

Figure 2

The figure provides an overview on critical components to be included in multimodale virotherapy-based therapies that work like prime-boost strategies.