Early Cancer Vaccine Results Are Promising
An experimental colorectal cancer vaccine designed to enlist the immune system in killing tumor cells is showing promise in an early clinical trial.
British researchers developed the vaccine from antibodies cloned from a patient with advanced colorectal cancer who survived many years longer than expected. When given to 67 colorectal cancer patients (average age 66), the vaccine stimulated immune responses in 70 percent, researchers say.
The findings are published in the Nov. 15 issue of the journal Clinical Cancer Research.
"This is the first vaccine shown to stimulate TNF-alpha — an immune-system protein that is very effective at killing cancer cells," says immunologist Lindy Durrant, Ph.D., who developed the vaccine.
Once one of the most promising fields in cancer research, vaccines designed to treat patients with existing cancers have been slow to emerge. Despite several decades of study, none has been proven to prolong the lives of cancer patients.
Durrant, who is a professor at the University of Nottingham in England, tells WebMD that she has been working on the colorectal cancer vaccine for about 10 years.
The vaccine is designed to work by stimulating the production of immune cells called T-cells, which in turn produce immune system proteins called cytokines that destroy cancer cells. Because cancer cells are so slow to grow, the body does not usually recognize them as a threat and does not mount an immune response to them.
"We have been working on ways to re-educate the immune system or essentially trick it into recognizing cancer cells early on," Durrant tells WebMD.
Her vaccine was derived from a colorectal cancer patient who survived for seven years after cancer had spread to his liver.
"This is very unusual as most patients die within one year of getting liver metastases," Durrant says. "I thought if this antibody helped this patient, if we could clone it, it might help others."
The cancer patients included in the trial were immunized both before and after undergoing surgery to remove their primary tumors. Of the patients treated repeatedly with the experimental vaccine, just over two-thirds appeared to exhibit measurable immune responses. Nineteen of the patients died during two years of follow-up, but the trial was not designed to study the effect of the vaccine on survival.
Durrant says she hopes to find funding for a larger, longer study with survival as an end point.
A vaccine expert who reviewed the study for WebMD says the failure to include detailed information on patient outcomes is troubling.
"Even if survival was not the endpoint, it is surprising to me that these researchers did not include more information about what happened to these patients," says Hildegund Ertl, M.D., of Philadelphia's Wistar Institute. "The fact that they didn't suggests there wasn't much to talk about."
Ertl says the development of cancer-treatment vaccines has gotten ahead of the science, and that is why the clinical trials have generally been disappointing.
"We need to know more about the immune system and how it is regulated before we can devise vaccine treatments that work," she says. "We have learned a lot over the past few years. That knowledge should be used to try and make existing vaccines better."
SOURCES: Durrant, L. Clinical Cancer Research, Nov. 15, 2006; Vol. 12: online edition. Lindy Durrant, Ph.D., professor of immunology, University of Nottingham, England. Hildegund Ertl, M.D., professor of immunology, Wistar Institute, Philadelphia.
By Salynn Boyles
Reviewed by Louise Chang, M.D