Cancer study points to vaccine

by Joseph Singh | 11/28/10 11:00pm

The answer to curing cancer may lie in the capabilities of the human immune system as opposed to current chemical treatments, according to a new study published by researchers at Dartmouth-Hitchcock Medical Center. The study, published Nov. 15 in Clinical Cancer Research, used tumors found in cancer patients to develop individualized vaccines that induce immune responses to cancers.

The research centers around dendritic cells immune cells that constitute part of the human immune system, according to Richard Barth, the principal investigator for the study. Dendritic cells locate and alert the immune system to antigens in the body, allowing it to fight off disease. Researchers developed individual vaccines for patients with colon or rectal cancer, using proteins from the tumors and dendritic cells grown from patients' blood samples, he said.

"What we're trying to do is boost or develop a new immune response against these cancer cells by providing a sort of strong signal in the form of a dendritic cell vaccine to the immune system," Barth said. "We're trying to stimulate what might have been in patients just an inadequate immune response to this tumor initially."

Barth performed tumor removal operations on 26 patients with colorectal cancer to reduce the scope of the cancer in each patient and increase the potential effectiveness of the vaccine. The vaccine, delivered to patients a month after surgery, showed positive results in the majority of cases, the study found.

Previous studies exploring the same topic have been largely ineffective because of the magnitude of the tumors the dendritic cell vaccines have tried to combat, according to Barth.

"Most of the studies in patients have used dendritic cells as vaccines to treatment patients that had large measurable tumors," he said. "The thing that we're doing in this study that's specifically different is that we're trying to treat patients when their tumor burden is minimal."

Colon or rectal cancer commonly spreads to the liver, requiring a surgery to remove the cancers called metastases which is only successful one-quarter to one-third of the time, Barth said. The low success rate is due to microscopic tumors present in the liver or lungs at the time of surgery, which subsequently grow to lethal sizes.

The purpose of the study was to look at the dendritic cell vaccine treatment's effect on cancer patients with tumors less than one half-millimeter in size.

"What we're trying to do with the vaccine is to treat tiny tumors, like those where the magnitude of the immune response that we can generate with a vaccine like this might be commensurate with that level of tumor burden," Barth said.

The study examined two main questions. The first was whether or not the vaccine would induce an immune response in patients by provoking T-cells, a type of white blood cell that fights invading cells such as tumors. Sixty percent of those who received the vaccine generated an anti-tumor response a surprisingly good outcome, Barth said.

The second question concerned the level of survival without the recurrence of cancer in patients whose immune systems responded well to the vaccine. After five years, 63 percent of those whose bodies generated responses to the vaccine no longer had any tumors. During the same period, only 18 percent of those whose bodies did not respond to the vaccine survived recurrence-free, according to the study.

"That is not something that has been shown by others in dendritic cell vaccine work," Barth said.

Barth said that alternative explanations for the success of the vaccine such as the potential prevalence of smaller metastases in those who responded positively to the vaccine hold little weight.

"You can't explain this based on clinical differences," he said. "If you look at the clinical characteristics of those who had immune responses compared to those who didn't, there was no difference between the two groups."

More work remains before the vaccine can be delivered outside of clinical trials, however.

"This study isn't definitive enough for us to say that everyone with colon cancer that spreads to the liver should get the vaccine," Barth said. "A next possible step would be to compare this vaccine with just dendritic cells which have not been pulsed with tumor antigens as a control."

The results of the study are "very suggestive" that the treatment will become a potential vaccine, according to Barth. The individualized nature of treatment makes it very appealing for treating the varying manifestations of cancer in different patients.

"This is a non-toxic treatment, and it's a personalized treatment," he said. "Some of the chemotherapy that is given to cancer patients is non-specific."

Barth was one of seven researchers credited with the study.