BioCanRx supports innovative clinical trial combining experimental cancer-killing viruses and antibodies

More than 50 Canadians with lung cancer could be the first trial participants who may benefit from a promising new combination therapy with the potential to significantly improve treatment outcomes, and cause fewer side effects than many current treatments.

Sponsored by Turnstone Biologics, with funding support from BioCanRx (Biotherapeutics for Cancer Treatment), the clinical trial will test a unique combination of immunotherapies involving the therapeutic antibody pembrolizumab along with Turnstone’s novel oncolytic virus MG1-MAGEA3, to potentially deliver a one-two punch in beating back cancer. Turnstone’s virus platform was jointly discovered and developed over the last 15 years by BioCanRx Scientific Director John Bell (The Ottawa Hospital and University of Ottawa), David Stojdl (CHEO and University of Ottawa) and Brian Lichty (McMaster University).

On its own, Turnstone’s virus technology generates a two-pronged effect on tumors by functioning both as a tumor-destroying oncolytic agent and as an immune-stimulating vaccine directed at specific cancer antigens such as MAGE-A3.  The result should be a potent immune response and strong anti-tumor activity, and has proven very effective in multiple preclinical models.

“We found that when normal cells become cancerous, it’s like they are making a deal with the devil,” explains Dr. Bell, a pioneer and leader in using viruses to combat cancer. “They acquire genetic mutations that allow them to grow very quickly, but these same mutations also make them more susceptible to viruses.”

What makes this new trial a world-first is that it layers on top of the virus therapy a cancer drug using antibodies known as immune checkpoint inhibitors. “We believe our viral therapy, has a tremendous chance to be successful,” says Sammy Farah, Turnstone’s CEO who is a veteran vaccine executive with extensive technology and product development expertise. “We are building and testing our technology alone and in combinations to find the best treatment options,” says Dr. Farah. “When our technology is paired with these checkpoint inhibitors, we see a better immune response and, as a result, the combination can be more effective at killing cancer cells in certain situations.”

Viral therapies are part of an emerging field of cancer research that uses immune cells, antibodies and viruses to attack cancer cells and, unlike chemotherapy and radiation, avoid healthy cells. This approach helps the immune system recognize and attack cancer on its own. It is also thought that immunotherapies could enable long-term protection from a cancer’s return.

So far the Canadian-engineered viruses have shown good results in shrinking tumours in animals and in human tumour samples. Those early successes have attracted serious interest from potential investors. Late last year, Turnstone raised US $41-million in Series B investment from US venture capitalists Versant Ventures, OrbiMed, F-Prime Capital, and Toronto-based FACIT.  These funds support the ongoing clinical trials as well as expansion of the company’s stable of products to include prostate and HPV-related cancers.

To accelerate progress in this emerging field of cancer immunotherapies, Dr. Bell and his colleagues launched the $60-million BioCanRx network in 2015, building on Canada’s global leadership in oncolytic viruses by connecting with the development of antibody and cell therapies.

That same year also marked the beginning of the first clinical trial to test this oncolytic virus immunotherapy on its own, a project that expects to enrol into the trial about 70 patients at sites across Canada. Like this combination trial, it uses engineered versions of the Maraba virus, isolated from Brazilian sandflies, and the Adenovirus, which causes the common cold. However, instead of only lung cancer patients, the current trial is testing the approach in patients with advanced or metastatic solid tumours.

“BioCanRx funding is supporting tests critical to understanding how the therapies affect the cancer and stimulate the immune system,” says Dr. Lichty, Chief Technology Officer at Turnstone.

BioCanRx also supports pharmaceutical-grade facilities at The Ottawa Hospital and McMaster University that manufacture the engineered Maraba virus and adenovirus respectively. Having a homegrown source for the viruses is more economical than purchasing them from abroad.

“BioCanRx has been an invaluable partner in helping the founding scientists and academic institutions advance the technology to a point where investors could be brought in,” says Dr. Farah. “We look forward to continue working with BioCanRx as we begin to test this combination therapy, which could provide new hope to patients with lung cancer, but also prove useful for all forms of cancer.”