FRIDAY, Oct. 7, 2005 (HealthDay News) -- For years, studies that focused either on cancer vaccines or anticancer drug therapies have proceeded along two separate tracks.
That's because chemotherapy usually weakens the immune system, so combining it with vaccines -- which rely on a strong immune response -- just did not make sense.
However, new research in mice may be changing that view.
A European study "is 'proof of concept' that the two treatments -- immunotherapy and chemotherapy -- can work together," said Dr. Richard Childs, a senior investigator at the U.S. National Heart, Lung, and Blood Institute and co-author of a commentary on the study, published in this week's issue of the Journal of the National Cancer Institute.
"It's a different way of thinking," Childs said. "It's looking at the problem and thinking 'Hey, there can actually be a synergistic effect of the two treatments, where the chemotherapy, in the process of killing the tumor, is also altering it to make it more susceptible to the immune system.'"
The study was led by Dr. Maria Cusi of the Siena University School of Medicine in Italy. Her team first inoculated healthy mice with a vaccine that primed their immune systems to recognize bits of a cellular protein called thymidylate synthase (TS) lying on the cancer cells' surface.
TS has long been a natural target for cancer vaccines because malignant cells tend to overexpress the enzyme.
However, the Italian team knew from previous trials that its vaccine might not work so work well on its own. What the researchers needed was an agent that could somehow enlarge the TS "bullseye" present on each tumor cell, to help the mouse's immune system recognize and destroy even more malignant cells.
They turned to a well-known chemotherapy agent called 5-fluorouracil (5-FU). The drug actually works by inhibiting expression of TS -- but before it does, cancer cells go through a period where they express much more of the enzyme.
"So, the researchers were changing the tumor by treating it with a drug that increases the expression of the target antigen, TS," Childs explained.
The mice were then injected with either breast cancer or colon cancer cells.
The result: In TS-immunized mice that also received the 5-FU chemotherapy, this combo treatment destroyed 43.5 percent of breast cancer cells, compared to a kill rate of just 26.5 percent in mice treated with immunotherapy alone. Results for mice injected with colon cancer cells were even better: 73.5 percent of the cancer cells were eliminated with the combo therapy versus 48.5 percent with vaccination alone.
Of course, a 73.5 percent kill rate is still a long way from the ideal, 100 percent. Another cancer researcher, Dr. Paul Chapman, said he was less than impressed by the findings.
"There's a long way to go before they could bring this to a clinical trial," said Chapman, who is head of the melanoma section at Memorial Sloan-Kettering Cancer Center in New York City. "It's an idea worth pursuing, but it would be more impressive once there's more data, and other tumor systems were looked at that are a little less artificial."
Childs agreed that the mouse model used in this study didn't mimic the experience of real-life human patients, because the mice received the combo therapy before they were injected with the cancer.
"Humans don't come to see the doctor before they have cancer, they come after they have cancer," Childs said. "They'll need to establish a model first where the mouse already has the tumor and then gets the treatment." Human trials are much further off, he said.
Still, the fact that two therapies once thought to be incompatible can form an additive, therapeutic "synergy" remains an exciting finding, he said.
"It's a one-two punch," Childs said. "My prediction, based on this study, is that we'll start to see a lot more studies investigating how we can use these two treatment modalities together."
More information
Learn more about cancer vaccines at the National Cancer Institute.
