Cancer Vaccine Research Gets a Boost

An existing drug thwarts a tumor's ability to trick immune system, researchers say

FRIDAY, Nov. 25, 2005 (HealthDay News) -- Moving closer to the elusive goal of a cancer vaccine, U.S. scientists say they've neutralized a class of immune cells that usually impair vaccine effectiveness.

The researchers honed in on "regulatory T cells" (called T-regs for short), which prior studies with mice and in labs have indentified as a major obstacle to the smooth functioning of "fighter T cells," commonly referred to as T cells.

Both cells play key roles in the immune response to disease.

However, while T cells leap into action to combat abnormal tissue -- such as a cancerous tumor -- T-regs actually inhibit T cell activity, preventing them from spinning out of control and inadvertently attacking healthy tissue.

Cancer cells throw this delicate cellular balance out of whack, boosting T- reg activity at the expense of a healthy T cell response.

But by using an already-approved lymphoma cancer drug, called Ontak, to eliminate T-regs in kidney cancer patients before administering a treatment vaccine, the study authors found they could vastly improve the patients' T cell count for the short-term.

With fewer T-regs, T cell production skyrocketed to as much as 1,000 times pre-vaccine levels.

In contrast, leaving T-regs alone meant T cell production grew to 50 to 100 times pre-vaccine levels.

The researchers hailed the novel combination strategy as a major theoretical advance in efforts to improve the treatment of many types of immune-suppressive conditions -- including a broad range of cancers.

"This is a one-two punch," said study author Dr. Johannes Vieweg, an immunology expert at Duke University Medical Center in Durham, N.C. "Now we have a means to boost the immune system by incredible amounts, so we are very, very excited to be the first to make this work."

Unlike routine inoculations, such as the polio and tetanus vaccine, the kidney cancer vaccine Vieweg and his colleagues are working with is not designed to immunize a healthy patient from developing the disease.

Instead, it is a treatment vaccine given to halt the growth of tumors in patients already diagnosed with cancer.

Working with 11 patients -- 10 with kidney cancer, and one with ovarian cancer -- the Duke team compared the results of vaccine treatment alone with vaccine treatment coupled with Ontak.

In the Dec. 1 issue of the Journal of Clinical Investigation, the researchers reported that seven patients received one dose of Ontak (denileukin diftitox) four days prior to vaccination, while four other patients received just the vaccine alone, in three doses, spread out bi-weekly.

It was important to offer Ontak before -- not after -- vaccination, the researchers said, because post-vaccine administration could actually interfere with T cell production.

Lab analyses showed that Ontak reduced T-reg counts by between 26 percent and 76 percent, with no toxic effects on other cell functions.

As expected, patients on the Ontak-vaccine regimen saw their T cell counts continuing to rise over time to much higher levels than those seen in the vaccine-only group.

Vieweg's team noted, however, that T-reg elimination was not permanent, with 75 percent of these cells growing back within two months after Ontak therapy.

But they believe the combination strategy has real promise. "This is a profound feat, because it never has been shown before in patients," Vieweg said.

"The next step is to look at the clinical efficacy of the combo strategy," he said. "And what we are currently pursuing is to enhance the depletion levels further, so we have a more durable effect, because the suppressor cells quickly come back."

Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society, described the research as "important and valuable."

However, he cautioned that cancer patients should not view the vaccine under study, or any cancer vaccine, as something that can help them in their struggle today.

"In the bigger picture -- despite 30 years of extremely limited success -- many investigators still believe in the concept that we can develop an effective cancer vaccine," Lichtenfeld noted. "But there are so many approaches to the concept and so many different questions that have to be answered that it's very difficult. And I suspect we're going to commit ourselves to another 30 years to keep working on this."

"So, yes, they demonstrated that by using Ontak, they could decrease the specific T-reg cells and as a result of that they could see a better immune response in the patients to their cancer vaccine," he acknowledged.

"But what they did not do, and do not say, is that that necessarily helped the patients do better. And they had a very small number of patients," Lichtenfeld said. "So, I expect they will take this information and apply it in a clinical trial to figure out whether or not it really makes a difference."

More information

For more on cancer treatment, check out the American Cancer Society.

Related Stories

No stories found.
logo
www.healthday.com