Utilising Mosquito Salivary Factors to Augment Oncolytic Therapy in Solid Tumours

The global health burden of solid tumours, including Hepatocellular carcinoma (HCC) and melanoma, continues to increase annually. Due to the resistance of many tumours to conventional therapy, more efficient anti-tumour therapy is needed. Oncolytic therapy is a promising cancer treatment in which oncolytic viruses (OVs) are used to selectively infect and kill cancer cells, as well as indirectly promote anti-tumour immune responses and thereby enhance survival. However, there is an urgent need to increase their efficacy. Here, we propose a radically different approach to enhance anti-tumour immune responses elicited by OVs. Our group has identified a unique peptide, derived from mosquito saliva called sialokinin (SK), that induces rapid vascular permeability and influx of leukocytes. It is well established that this response acts to inadvertently enhance mosquito-borne virus infection, many of which have also been used as experimental OVs. Here, we hypothesis that intra-tumoural administration of SK will enhance; localisation of oncolytic virus to tumours; infection of tumour cells with virus; and the recruitment of leukocytes that aid both virus replication and activation of anti-tumour immunity. We report in vivo experiments that investigate whether SK or abiotic mosquito saliva modulates extent of two prototypic OVs and activation of innate immunity, in HCC and melanoma. SK was able to induce vascular leakage and oedema in skin and lower doses of SK recruited leukocytes in a dose dependent manner. Interestingly, we found that although virus infection was not robustly enhanced by salivary factors in tumours, induction of innate immune responses including CD8 T cell recruiting chemokines were enhanced by mosquito saliva. Moreover, mosquito saliva was able to upregulate co-stimulatory molecules on dendritic cells (DC) and antigen presentation to antigen-specific cytotoxic T cells. Together, we show that there is potential in utilising immune modulating peptides from mosquitoes to enhance host immune response to OV therapy.