Viruses are great tools to help understand how the anti-tumour immune response works, say researchers.
The USFDA approved talimogene laherparepvec (T-Vec), the first oncolytic virus therapy, to treat melanoma in 2015. It is based on a genetically modified form of a herpes simplex virus type 1.
T-Vec is injected directly into a tumour. As the virus makes more and more
copies of itself, it causes cancer cells to burst and die. The dying cells release new viruses and other substances like tumour antigens that can cause an immune response against cancer cells throughout the body.
Although this virus can infect both cancer and normal cells, normal cells are able to kill the virus while cancerous cells cannot.
Now, researchers are trying to enhance the immune response to the tumour by combining oncolytic virus therapy and immunotherapy.
One of the trials conducted on nearly 200 patients found that T-Vec, with the checkpoint inhibitor ipilimumab, induces an immune response.
A second trial combining T-Vec with pembrolizumab in 21 patients induced infiltration of T cells into tumours that had low levels of these cells prior to treatment.
The study suggests that viral therapy can change the local microenvironment to make an immunologically “cold” tumour lacking T-cells — into an inflamed, or “hot,” tumour.
Also underway is a phase 3 clinical trial involving 600 patients with melanoma who will receive T-Vec with or without pembrolizumab.
T-Vec has already been studied for different cancers including pancreatic, head and neck and soft tissue sarcomas.
Duke Cancer Institute researchers have been testing an engineered poliovirus, called PVS-RIPO, in patients with glioblastoma. They observed very clear signs that the virus elicited anti-tumour immune responses.
A phase 2 trial testing PVS-RIPO with or without chemotherapy drug lomustine is also underway in patients with glioblastoma.