Are we finally making headway in the use of oncolytic viruses to treat cancer? Researchers say they’ve learned from past mistakes.
A tumour-attacking virus has achieved elimination of tumours in 64% of patients with bladder cancer who were unresponsive to conventional treatment, according to interim findings presented at the 24th Annual Meeting of the Society of Urologic Oncology (SUO) in Washington in December.
Patients will be tracked for a total of three years before full outcomes can be determined but, given the failure of the decades-long pursuit of positive outcomes for this treatment, this interim analysis is an exciting development.
Oncolytic viruses are supposed to work by infecting cancerous cells, triggering the immune system to flood the infected cancer cells with T cells that attack both the infection and the tumour. When the cancer cells burst, cancer antigens should be released, stimulating an immune response to identify and destroy cancer cells throughout the body.
The phase III trial is using modified adenovirus developed by CG Oncology in patients who have not undergone chemotherapy to strongly stimulate an immune response.
Sixty-six patients with bladder cancer which hadn’t penetrated the muscular wall were injected with the virus directly into their tumour and were assessed at three months and six months. Tumours were undetectable in 76% of patients at one or more of these assessments, and in 74% the tumour had not returned at the six-month point.
Previous trials have often tested these treatments on immunocompromised patients who were unable to muster an immune response to the therapy. Without being able to rile up the immune system and rally T cells to the tumour, treatment was unsuccessful and oncolytic viruses continued to be a failure in cancer therapy.
Researchers in the past, fearful that this radical treatment may not be safe, also often used weakened viruses which failed to provoke adequate immune response.
But researchers have not given up on oncolytic viruses. Globally, more than 90 clinical trials are currently underway or starting soon .CG Oncology completed a phase II trial in 2022 using checkpoint inhibitor pembrolizumab and found that combined with their modified adenovirus, they were able to eliminate tumours in 20% of bladder cancer patients, 68% of whom were still tumour-free a year after treatment.
The FDA has already approved one oncolytic virus – talimogene laherparepvec (T-VEC). But it failed to gain approval here, and that’s been a blow to the momentum in oncolytic virus research in Australia, Associate Professor Andrew Haydon, medical oncologist at the Alfred Hospital in Melbourne and adjunct senior lecturer at Monash University, told Oncology Republic.
Despite hopes, T-VEC failed to beat standard immunotherapy in both regression rate and overall survival.
“The biggest barrier to these treatments has been seeing positive effects away from where the virus has been injected. In the T-VEC trials for melanoma, we injected the virus directly into a tumour. The hope was that infecting that tumour would then stimulate the immune system to attack the melanoma more generally throughout the body. That didn’t happen,” he said.
Professor Haydon said the mode of administration used in the Australian trial was not ideal, and the end goal should be a systemic therapy.
“Most of these tumours that can be injected are not life-threatening; they’re not the liver or brain metastases. They’re the little tumours that you can get access to. The virus seems to work quite well in the tumour you inject but it doesn’t have the generalised systemic effect we were hoping for.”
Given how long it took researchers to create the effective immunotherapy used today, Professor Haydon said it may take quite some time before oncolytic virus research got there.
He hopes a positive outcome from this phase III trial will reinvigorate Australia’s enthusiasm for oncolytic virus research. For isolated bladder tumours, such as in this trial, Professor Haydon said oncolytic viruses could very well be effective.
“However, what we are looking for is a virus that you can get into the bloodstream so it can go everywhere in the body rather than just where you can get a needle into, and to determine whether it is safe to do that,” he said.
