Anti-tumour immunotherapeutic strategies represent a promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumour specific antigen(s) onto DCs, potentially represents one of the most advanced strategies to achieve effective anti-tumour immunisation.

In this study, we developed a DC-specific adenoviral (Ad) vector, named Ad5scFvDEC205FF, targeting the DC surface receptor, DEC205. The infectivity of this vector on DCs were 60% while that of other control vectors was less than 10%, demonstrating superior infectivity of DCs in vitro. Moreover, an average of 14% of DCs were infected by Ad5scFvDEC205FF-GFP, while less than 3% of non-DCs were infected following in vivo administration, demonstrating highly selective in vivo DC infection. To further optimise this viral vehicle for the systemic delivery of glioma specific antigen (CMV-IE), the hexon of this vector was replaced with that of Ad serotype 3, minimising coagulation factor X mediated liver sequestration and toxicity, named Ad5H3scFvDEC205FF-CMV-IE. Importantly, vaccinated group with this vehicle showed no signs of tumor until day 75, while the median survival of PBS treated group was 19 days in GL261^CMV-IE implanted murine glioma models (p<0.0007). Furthermore, when re-challenged, cancerous cells were completely rejected, suggesting the formation of long-term immunological memory against the tumour cells.

In conclusion, our novel, viral-mediated, DC-based immunisation approach has significant therapeutic potential for patients with high grade gliomas