Viruses may improve the success rate of immunotherapy treatments, according to two new studies.
It’s thought that viruses could be used to increase the proportion of patients who respond to immunotherapy drugs by drawing the attention of the immune system to the cancer.
“Immunotherapy is a very big and active area right now, especially with checkpoint inhibitors,” said Professor Alan Melcher, a Cancer Research UK-funded expert in virus cancer therapies at The Institute of Cancer Research, London.
Immunotherapy treatments provide a boost to the immune system so that it can recognise and destroy the tumour. But they don’t work for everyone.
“They work best in ‘hot’ tumours where there’s already some immune response,” he said.
Tumours have evolved mechanisms to evade immune recognition. But viruses are well recognised by the immune system.
The studies, one in 21 patients and the other in mice, injected viruses into ‘cold’ tumours that the immune system misses to make them ‘hot’.
The first study, by scientists from Johnson Comprehensive Cancer Centre in Los Angeles and published in Cell, included 21 patients with advanced melanoma. They received injections of a live oncolytic virus called T-VEC into the tumour, followed by treatment with the immunotherapy drug pembrolizumab (Keytruda).
Oncolytic viruses can infect and kill cancer cells, and T-VEC – a modified version of the herpes virus – is approved for treatment of melanoma that has spread and can’t be removed through surgery or treated with immunotherapy drugs alone.
Pembrolizumab is a type of immunotherapy called a checkpoint inhibitor that releases the brakes on the immune system.
Tumours in 13 patients responded to the combined treatment, more than would be expected with either treatment individually. 7 patients were deemed to have a complete response, meaning their disease was undetectable 4 weeks after treatment.
Melcher said that, although the study included a relatively small number of patients, the response rate when using the virus was very encouraging.
“They also see that there’s an increase in the ‘heat’ of the tumour when the virus is used – in line with the idea that the virus makes the tumour more susceptible to the immunotherapy,” he added.
Lead author Dr Antoni Ribas said: “We had a hypothesis about how these treatments would work together, and when we did biopsies of patients’ tumors we found that they were cooperating in just the way we thought they would.”
The second study is of unpublished work presented at an international cancer immunotherapy conference in Frankfurt.
Researchers injected active or inactive viruses into the tumours of mice with skin cancer, and bowel cancer cells in the lab. This was done in combination with a checkpoint immunotherapy drug.
The team, from Memorial Sloan Kettering Cancer Centre in New York, found that the inactive virus was safe in mice, and that it brought about a greater immune response than an active form.
Viruses under development as treatments are live, meaning they can replicate and kill cancer cells.
Inactivated viruses, such as the one used in the mice, are unable to replicate so can’t cause disease. But according to Melcher, active oncolytic viruses, such as those injected into the patients, are selected and modified to be safe.
“The Cell study raises the question of whether virus treatments for cancer have to be live or not,” he said.
The aim of early work involving viruses as cancer treatments was focused on using the viruses to kill the cancer cells directly. But Melcher says that their success may be for other reasons.
“These viruses may work mainly by stimulating an anti-tumour immune response,” he said. “It’s more widely accepted now that much of the anti-tumour activity of these viruses is by activating the immune system, rather than directly killing the cancer cells.”
Senior author Dr Liang Deng said the results support the injection of inactivated virus as a safe and effective cancer treatment, either alone or in combination with immune checkpoint blockade drugs.
Ribas, A. et al. (2017) Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy, Cell
Dai P et al. (2017) The combination of intratumoral injection of inactivated MVA and systemic delivery of immune checkpoint blockade leads to eradication of large established tumors and distant tumors. CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference