Grant: Travel Awards - Institute Community Support

Two in five Canadians will develop cancer and 25% of those will die of this disease. Specialized immune cells constantly patrol our tissues and eliminate tumour or virus-infected cells. These natural killer (NK) cells are among the first cells to recognize and kill stressed or pre-cancerous cells to control cancer formation and its spread. However, constant stimulation and unfavourable conditions within the tumour microenvironment can render NK cells non-functional, favouring cancer persistence. Current NK cell immune therapies are costly and are not widely available, thus a generalized NK cell-based treatment with the capability for specialization would be greatly advantageous. Recently, NK cells have been identified with memory-like properties and kill cancer and virus-infected cells with more potency than conventional NK cells. Currently, the only known instance of memory NK cell formation is during human cytomegalovirus (HCMV) infection, thus we aimed to determine the factors present during viral infection that drive NK cells toward memory-like NK cells. We found that the cmvIL-10 'virokine', a soluble messenger protein encoded by HCMV, enhanced NK cell killing up to two-fold over control conditions. Killing is enhanced through a specific NK cell surface protein, CD16, with a specialized ability to recognize target cells coated with antibody. Enhancing NK cell activity with cmvIL-10, in combination with current monoclonal antibody therapies available for cancer (i.e. ritixumab, lirilumab) would provide specificity whilst retaining adaptability. This virokine would also reinvigorate NK cells that have been rendered non-functional. This approach would provide a cost-effective, widely available therapy that can be specifically directed towards many tumour types to reduce malignancies and prevent cancer spread.