Researchers harness power of viruses to fight cancer

Researchers are cautiously optimistic about a brain cancer treatment involving a virus being tested at the MUSC Hollings Cancer Center. Neuro-oncologist David Cachia, M.D., said he doesn’t want to raise false hope, but he is fascinated by the possibilities.

“It hasn’t been tried before, so we’re hoping that this might be the breakthrough that we’ve been waiting for, for a long time,” Cachia said.

The lab-created virus is similar to a poliovirus used in a study whose results were featured on the CBS show 60 Minutes. That study, out of Duke University, found that infecting tumors with re-engineered polio caused them to shrink in some cases.

“They work on the same principle,” Cachia said. “One of the differences is that our study is at a further advanced stage of development compared to the polio study.”

The MUSC Hollings Cancer Center study, which is part of a national clinical trial called Toca 5, combines a virus with an antifungal drug to fight recurrent glioblastoma and anaplastic astrocytoma, which are aggressive malignant brain tumors. 

It’s part of a wave of virus-driven immunotherapies. “A lot of trials are trying to harness the power of the immune system,” Cachia said. “The immune system doesn’t recognize cancer in the brain. The idea is to tell it, ‘Hey, there’s something wrong over here.’”

Phase 1 of the research showed the treatment was safe for the small number of patients it included. Twenty-seven people with recurrent, high-grade gliomas who received a higher dose of the drug had a median overall survival rate of 14.4 months, with a 40 percent chance of surviving 24 months. 

“Those are remarkable numbers for patients with these type of tumors,” Cachia said.

Phase 2, which is where the research has shifted to now, tests it on a larger number of patients. Thirty-three top cancer treatment sites, including the MUSC Hollings Cancer Center, are involved. Cachia has enrolled three brain cancer patients so far, and hopes to add more.

The treatment involves two steps. First, it uses the lab-created virus Toca 511 to try to jump-start the immune system to go after malignant tumors. The virus is injected into the brain when the surgeon removes the tumor, ensuring the virus gets past the blood-brain barrier that can sometimes prevent treatments from reaching their targets.

This is no ordinary virus, Cachia said. Developed by the gene therapy company Tocagen, it’s genetically modified to incorporate a special gene called cytosine deaminase. The gene allows infected tumor cells to convert an antifungal medication taken by mouth into a potent chemotherapeutic agent. 

The advantage is that only the infected tumor cells will be exposed to the chemotherapy since the rest of the body’s cells won’t convert the antifungal to chemotherapy – they don’t have the gene to make this conversion. The rest is done by the immune system that then targets the infected tumor cells. 

Brain cancer can progress quickly in some cases, Cachia said. “Unfortunately, with more malignant brain tumors, the outcomes are poor. Despite treatments, most patients survive 14 to 16 months.”

But research is giving doctors a better idea of what they’re dealing with. “In the last few years, there has been a lot of improvement in understanding the molecular characteristics of these tumors. Now, we need to better understand the biology of these tumors.”

Cachia said the Toca 5 clinical trial may help in that understanding. “I think being realistic is important. We’re trying to raise the bar, but we don’t want to raise false hope.”

Cachia’s research isn’t the only work at MUSC involving the use of a virus to try to kill cancer cells. Eric Bartee, Ph.D., a microbiology and immunology specialist, is exploring whether the myxoma virus, which is the equivalent of smallpox for rabbits, can kill myeloma cells in humans. Myeloma is a cancer that starts in the bone marrow.

“Myxoma preferentially binds to malignant myeloma cells and then causes those cells to commit suicide,” Bartee said. 

So far, it’s only being tested in the lab, not on humans.

“We would love to use it as a treatment one day,” Bartee said. 

He’s testing two ways of using the virus to fight cancer. One involves injecting it into the bloodstream, which causes the virus to kill the cancer cells in the bone marrow and causes the immune system to kick and fight the disease too. 

The other method uses the virus in the context of an existing treatment known as autologous stem cell transplant. “In this treatment, patients’ bone marrow is removed and treated with myxoma, then transplanted back into the patient,” Bartee said. “That way, the virus kills the myeloma cells but leaves the other cells intact, preventing a myeloma relapse.”

Bartee said that method is promising but a myxoma virus that can be used in people, not just in the lab, is needed for it to work.