Vaccine Shows Some Promise Against Advanced Cancers

But only a minority of patients benefited and more work may need to be done, experts say

Monday, August 2, 2010
 
MONDAY, Aug. 2 (HealthDay News) -- Scientists have genetically tweaked a virus to fashion a therapeutic vaccine that appears to attack a variety of advanced cancers.
 
The vaccine has provoked the required tumor-fighting immune response in early human trials, but only in a minority of patients tested.

And one expert urged caution. "They were able to generate an immune response [with the vaccine]. That's a good thing but we need a little more information," said Dr. Adam Cohen, assistant professor in medical oncology at Fox Chase Cancer Center in Philadelphia. He was not involved in the study.

"This is the first study in cancer patients with this type of vaccine, with a relatively small number of patients treated so far," Cohen noted. "So while the immune response data are promising, further study in a larger number of patients will be required to assess the clinical benefit of the vaccine."

One vaccine to treat prostate cancer, Provenge, was recently approved by the U.S. Food and Drug Administration. However, Cohen noted that many other cancer vaccines have shown early promise and not panned out.

The theory behind therapeutic cancer vaccines is that people with cancer tend to have defects in their immune system that compromise their ability to respond to malignancy, explained study lead author Dr. Michael Morse, associate professor of medicine at Duke University Medical Center.

"A vaccine has to work by activating immune cells that are capable of killing tumors and those immune cells have to survive long enough [to] get to the tumor and destroy it," he explained.

For this vaccine, the authors used the Venezuelan equine encephalitis virus, an "alphavirus" that affects the nervous systems of equines, including horses and donkeys.

Alphaviruses provide an attractive vector for vaccines because they naturally seek out dendritic cells, which stimulate the body's immune system.

In their work, the authors removed the innards of the virus and substituted instead a gene for the carcinoembryonic antigen (CEA). This immune system biomarker is overproduced in many different types of cancer.

The vaccine was then administered multiple times over a period of three months to 28 patients with advanced, recurrent forms of lung, colon, breast, appendix or pancreatic cancer. The participants had already failed several rounds of standard chemotherapy.

Five patients displayed a response to the therapy: Two who had already been in remission stayed in remission; two patients saw their cancers stabilize; and a liver lesion in one patient with pancreatic cancer was no longer evident.

The responses tended to occur in patients with smaller tumors and in those receiving higher doses of the vaccine.

The alphavirus-based vaccine also managed to evade the immune system's regulatory T cells, which could have shut down the body's immune response, the researchers said.

Although T cell levels were elevated in some patients, the vaccine was able to get around them.

Co-authors included employees from Alphavax, which develops new vaccine technology. The study was partially supported by the U.S. National Cancer Institute.

SOURCES: Michael Morse, M.D., associate professor, medicine, Duke University Medical Center; Adam Cohen, M.D., assistant professor, medical oncology, Fox Chase Cancer Center, Philadelphia; Aug. 2, 2010, Journal of Clinical Investigation, online

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