When people with stage 1 bladder cancer relapse after standard treatment, often the next step is to remove their bladders. Now a University of Florida Health researcher is testing whether a modified version of the common cold virus could prevent this step, or even cure the disease.
About 74,000 people in the United States are diagnosed with bladder cancer annually, according to the National Cancer Institute, and the cancer recurs at rates ranging from 30 to 80 percent, said Paul Crispen, M.D., a urologic oncologist with UF Health and an assistant professor in the UF College of Medicine’s department of urology. He is working with a company called Cold Genesys to open a clinical trial using a modified cold virus to kill cancer cells in the bladder.
The treatment being tested showed promise in fighting bladder cancer during a phase 1 study evaluating the safety of the treatment. While patients can relapse afterward, the method may offer better response rates than currently available medications, and researchers are studying ways to hone the treatment.
Physicians commonly treat patients with stage 1 bladder cancer by placing chemotherapy drugs within their bladder through a catheter. However, when the bladder cancer continues to recur following these treatments, physicians often recommend bladder removal. While bladder removal can cure patients with stage 1 bladder cancer, the surgery also results in dramatic changes in their quality of life.
“The most interesting aspect of this trial and the reason we have a lot of patients interested in participating is that this is a method that may allow a patient to keep their bladder in place,” Crispen said.
Now, Crispen and Cold Genesys hope that the modified cold virus could prove effective against bladder cancer and potentially decrease the chance of bladder removal. The virus is loaded directly into the bladder through a catheter, and is designed to replicate only within cancer cells, killing them.
The modified adenovirus is equipped with what’s called an S-1 promoter, which triggers the virus’ DNA to tell the virus to begin replicating within cancer cells. That causes those cells to burst open and release more viral particles, said Dominic Curran, M.B.Ch.B., the associate medical director for Cold Genesys.
The injury to the cells also prompts the cells to release cytokines, which are proteins involved in the immune response that help activate the immune system to further attack cancer cells.
“Because of the way it’s designed, the cold virus only affects mutating cells,” Curran said. “It’s designed to not infect normal, healthy cells.”
The initial phase 1 trial that examined the virus showed promise in a small group of people who were treated. Thirty-five patients received single or multiple treatments of the adenovirus at one of four dosage levels to assess whether they could tolerate the treatment well. In a follow-up assessment, 48 percent of these patients had a complete response, or no evidence of cancer in a follow-up appointment, Curran said. Of the 11 patients who were given multiple doses, nine had a complete response to the treatment. However, the median duration of the response was 10.4 months in both the single- and multiple-dose groups. As with other bladder treatments in which drugs are delivered through a catheter, side effects were noted, including bladder irritation and fatigue.
Curran said the modified cold virus could be used in approaches for other cancers.
“It’s quite easy to catch the common cold, and we would like to harness that and adjust the virus to infect and replicate within the tumor cells of different types of cancer,” Curran said.
Author: Morgan Sherburne