Scientists have crafted an experimental vaccine against advanced ovarian cancer that was safe and triggered an immune response using muscled-up blood cells primed by tumors that were taken from the patients.
It took 7 days to make the injection individually for each woman, according to a report today at the American Association for Cancer Research meeting in Washington. The therapeutic vaccine was the first step in a two-part process that involved teaching the woman’s blood cells to recognize the cancer, then infusing an army of her own infection-fighting immune system cells to attack the tumor. The study was the first clinical trial of this new approach.
While the research in 31 patients wasn’t large or long enough to prove they all did better than with traditional care, 19 showed positive responses, said Lana Kandalaft, director of clinical development at the Ovarian Cancer Research Center at the University of Pennsylvania in Philadelphia. One woman who had suffered several previous relapses before treatment remains cancer-free after almost four years, defying expectations.
“We are preventing progression of already existing disease,” said Kandalaft, the study’s lead researcher, in a telephone interview. “Most of the patients are now on maintenance vaccine, just to keep the system going. We haven’t seen them recur. We are seeing how long they can go.”
Ovarian cancer is often caught late, making it hard to treat. It kills more than 14,000 women in the U.S. each year, making it the fifth deadliest cancer.
There was no comparison group used in the research, and some patients have only been followed for a few months. Still, the tumors normally resume growing within months, with death expected for most women within two years, Kandalaft said.
“For some patients, it’s a dramatic difference,” she said. “For others, we cannot say if it’s better than the standard of care that’s out there now.”
The vaccine was given in combination with Roche Holding AG’s Avastin, a commonly used drug for ovarian cancer that shuts off the blood supply to the tumor. Women were given repeated doses of the vaccine, as long as there was enough tumor tissue to make additional doses, to try to keep the cancer at bay.
The findings provide additional evidence that enhancing the immune system can play a role in fighting cancer, said Donald Trump, chief executive officer of Roswell Park Cancer Institute in Buffalo, New York. While the results should be considered cautiously, they will generate enthusiasm, said Trump, who wasn’t involved in the research.
“Exactly how this will shake out isn’t clear,” he said in a telephone interview. “It’s a preliminary study. But it’s an exciting time in immunology to be sure.”
The bespoke vaccine was crafted using each woman’s tumor and blood. Blood cells were manipulated in a laboratory to develop into dendritic cells, which normally detect foreign invaders and marshal the immune system. The living tumor was treated with chemicals to make it more immunogenic, exposing its potential weaknesses.
Finally, the tumor cells were added to the dendritic cells, priming them to set off an immune system alarm if they detect cancer. The treated dendritic cells are sent back into the body to lead the immune system’s fight against the cancer.
“The dendritic cell is completely ready to educate the T-cells in the body to recognize the tumor,” Kandalaft said. “We made it easier for them, by telling them what to do.”
The women were given the vaccine after surgery to remove all of their cancer. Seven of the 19 patients who responded to vaccination with the treated dendritic cells had no measurable disease at the end of the study.
The remaining 11 patients went to the second-stage of the trial. Their infection-fighting T-cells were removed three months after the vaccination, expanded and made more active, then returned to the body to resume fighting the cancer. Seven of those patients had stable disease, while another had a complete response that temporarily ridded her body of cancer. It subsequently returned, and she died last year, Kandalaft said.
There were almost no side effects, she said. Trump cautioned that risks from immune therapy can develop later.
“We have to remember that the goal of immune therapy is to establish an immune response against the cancer,” Trump said. “It may sometimes turn out that the immune response acts against the cancer as well as human tissue. It’s not safer than other therapies, it’s just the toxicities are going to be a little different.”