Combination cytotoxic immune effector cell and oncolytic virus therapy for cancer therapy

Certain viruses have been shown, in the laboratory, to be able to kill cancer cells. These viruses are not normally damaging to humans and don‘t generally cause significant illnesses. Some cancer cells have lost the ability to eradicate viruses in the way that healthy cells can, so that these viruses can be used to target and selectively kill cancer cells in patients. We are trying to improve the effectiveness of this approach by studying different viruses, and by combining the viruses with cells from the body‘s own immune system which themselves can attack cancer.
Combining cell and viral therapy for cancer is an exciting new approach to cancer therapy. Critically, this research is focused on testing cells and viruses using human reagents, including tumour cells freshly resected from patients; this ensures that our work is of maximum relevance to the disease as seen in patients, and helps rapid translation of our findings into early clinical trials. We‘re specifically looking at melanoma; an aggressive form of skin cancer that kills thousands of people, particularly young people, each year, and for which there is little effective treatment. We hope our research will also benefit other cancers too.

Oncolytic viruses (OV) are being investigated both for their ability to directly kill cancer cells, and for their role as immunogens, stimulating bystander innate and adaptive anti tumour immune responses. Reovirus (RV) and measles virus (MV) can cause immunogenic tumour cell death, and are already in early clinical trials. Cytotoxic immune effector cells (LAK, NK, CIK, CTL) may potentiate viral therapy, by combining direct cell-mediated killing with an ability to carry (hitchhike) OV, and hand them off to target tumour cells. My aim is to study the combination of immune effector cells and OV as a novel human anti-cancer therapy suitable for clinical translation. I will study the direct innate cytotoxicity of immune effector cells, and direct killing by RV and MV against melanoma, using both cell lines and autologous systems of freshly resected tumour. Combined OV hitchhiked on immune effector cells will then be tested for direct cytotoxicity and activation of anti-tumour immunity. Finally, the effect of cell carriage on protection of OV from neutralising anti-viral antibodies, potentially enhancing in vivo efficacy, will be explored.