Dr. Hideho Okada, a cancer vaccine researcher, stands in his office at the Hillman Cancer Center at UPMC.
By Mark Roth Pittsburgh Post-Gazette
One of the persistent frustrations in cancer treatment has been the way that tumors can evade our immune systems as they grow and multiply inside our bodies.
Even though cancer cells have special surface markers, known as antigens, the body often doesn't seem to be able to mount a full-fledged attack against the tumors, and the longer they last, the more they seem to suppress the immune response.
Yet it doesn't have to be that way, says a dedicated band of scientists in universities and companies around the globe. In fact, they say, we may be on the verge of being able to vaccinate people against cancer in the same way we do with infectious diseases.
"I think we really are on the cusp of a revolution in cancer immunology," said Andres Salazar, CEO of Oncovir, a Washington, D.C., company that makes an immune system booster for cancer vaccines. "We hope to make patients allergic to their cancers."
The first commercial cancer vaccine out of the gate is likely to be sipuleucel-T, a vaccine against advanced prostate cancer being made by Dendreon Corp. of Seattle, Wash.
Not far behind in the pipeline is Stimuvax, a vaccine being made by Merck in Germany that targets a cancer marker known as MUC1, which is present in many different tumors.
That is the same target that University of Pittsburgh researcher Olivera Finn has developed her own vaccine against.
Dr. Finn's vaccine, which has been in development for several years, has already shown limited success in advanced pancreatic cancer patients.
But because she believes these vaccines will work best in people who do not yet have cancer, she and UPMC researcher Robert Schoen are testing the vaccine now in patients who have precancerous polyps in their colons, to see if it prevents the onset of colorectal cancer.
While she is still a couple years away from being able to report results, Dr. Finn knows the vaccine has created a strong immune response in the patients and has had few side effects.
The hope? "If we immunize early on, the cells that become abnormal might actually be eliminated by a strong immune response," she said.
James Gulley, a leading vaccine researcher at the National Cancer Institute, agrees with that approach. He said there is growing evidence that the immune system doesn't work as well against cancers that are more advanced, which "leads me to believe the best time to try vaccines thus might be before the tumor gets too large."
That is also the goal of a new cancer vaccine trial being started here for patients with gliomas, a type of brain cancer.
That experiment, being run by UPMC neurosurgeon Hideho Okada, will administer the first vaccine ever developed for low-grade gliomas, which includes an immune system booster called Hiltonol.
These cancers are especially insidious, Dr. Okada said, because they often grow slowly for several years and the patients look and feel healthy. Then suddenly, they convert into an aggressive form of brain cancer that kills the patients.
"A low-grade tumor is not a benign tumor," he said. "Unfortunately, a diagnosis with a low-grade glioma today is still a death sentence" -- something he hopes the new vaccine can reverse.
The trial will be small to start with, involving 18 patients with new cancers and nine with recurrent tumors.
"We believe that immunotherapy could be long-lasting," Dr. Okada said. "The actual drug doesn't have to be present in the system, unlike chemotherapy, and the slow-growing nature of these gliomas gives us sufficient time to vaccinate and revaccinate patients.
"Our goal is to educate the immune system so that it recognizes the cancer-specific antigens."
A key part of that will be the Hiltonol booster made by Dr. Salazar's company.
The substance, named for co-inventor Hilton Levy, mimics the RNA of a virus, and seems to deliver a "warning signal" that fires up the immune system, Dr. Salazar said. It is being used now in about 12 different cancer vaccine trials, he said, including Dr. Okada's.
Hiltonol is made of double-stranded RNA, "which doesn't normally occur in mammalian cells," he said, "but is a product of viral replication, so when mammalian cells see it, they say, 'There's a difference here.' "
Besides monitoring the patients who had colon polyps, Dr. Finn has also reported encouraging results with her vaccine in specially bred mice.
The mice have human genes that make them prone to get inflammatory bowel disease, which is a known risk factor for colorectal cancer. In fact, if they are left untreated, she said, about 80 percent of the mice will go on to get cancer.
When her team administered the MUC1 vaccine to the mice, though, not only did far fewer of them get inflammatory bowel disease, but almost none of them went on to get cancer.
The encouraging results of MUC1 vaccines aren't confined to animals.
The version that is now being tested by Merck showed a 17-month survival advantage for advanced lung cancer patients who got the vaccine vs. those who didn't in an earlier trial.
While the current testing has been suspended temporarily because one patient got encephalitis, the man whose company invented the vaccine is encouraged by the progress it has made.
Robert Kirkman, president of Oncothyreon, the Seattle, Wash., company that developed the vaccine, said he understands the logic of testing cancer vaccines on patients who aren't as sick, but said that presents a financial challenge.
If vaccines were to be tested on a large group of patients with earlier stage cancer, it could mean following them for up to 10 years to see if the therapy was effective, and that would be enormously expensive.
If his company's vaccine, Stimuvax, demonstrates a relative survival benefit for patients with later-stage cancers and can then be approved as a commercial product, he said, "it's likely the work will then be done to show it works in earlier-stage disease, but it's much easier to do that after you've got a revenue-generating product."
The National Cancer Institute's Dr. Gulley said he thinks there may be a middle ground between what is "biologically plausible and financially feasible" for testing cancer vaccines on human patients.
There is evidence that cancer vaccines take longer to show beneficial results than other kinds of therapies, he said, partly because the immune system needs time to gear up to fight the tumor.
In doing human trials of vaccines, he said, "if I were to err on one side or the other, I'd err on the side of what's biologically plausible." Too often in cancer treatment, "everyone's looking for the big payoff with little effort, and that's exactly the wrong thing to do."
One other possible benefit of vaccines: They may make it possible for some people to live with their cancers for many years, even if the malignancies aren't completely wiped out.
With Dr. Okada's brain tumor patients, for instance, it would be a major advance if a vaccine could just stop their tumors from becoming aggressive and life-threatening.
Even with the addition of newer forms of chemotherapy in recent years, doctors who treat gliomas have only been able to extend average life spans by about three months over the past couple of decades.
"So if I could even make brain cancer a chronic disease like hypertension or diabetes," he said, "I would be ecstatic."
Correction/Clarification: (Published Apr. 8, 2010) Olivera Finn is a cancer researcher at the University of Pittsburgh. Her affiliation was misidentified in this story on cancer vaccines as originally published Apr. 7, 2010.Correction/Clarification: (Published Apr. 10, 2010) A vaccine booster called Hiltonol is based on double-stranded RNA. This story on cancer vaccines as originally published Apr. 7, 2010 described its makeup incorrectly.