A syringe full of harmful bacteria sounds like the last thing a cancer patient needs. But a new study of dogs with tumors, and even a human cancer patient, shows that the injection of some bacteria directly into tumors may reduce or even eliminate. The results strengthen the case that the use of bacteria to treat cancer, an approach that performed poorly in some clinical trials, will work.
Doctors first noticed bacterial infections sometimes slowed or eradicated tumors there are more than 0 years. William Coley, a surgeon in New York, was the first to run with the idea. In the 180s, he began injecting cancer patients with living Streptococcus bacteria to fight against their tumors. After two recipients died from infections, it passed to the administration of dead bacteria and eventually treat more than 1,000 patients with so-called Coley toxins. Coley sometimes injected bacteria into tumors and sometimes in blood, and many of his patients survived. But treatments such as radiotherapy, chemotherapy and soon pushed approach Coley surgery in the history books. Yet a new analysis of some of its business in 1999 suggested his success rate was about the same as for modern cancer therapies.
Recent attempts to revive the treatment of cancer bacteria have run into obstacles. For example, a clinical trial in which patients received intravenous doses of weakened Salmonella bacteria found that the treatment was safe but had little impact on tumors. For over a decade, geneticist Bert Vogelstein cancer at Johns Hopkins University in Baltimore, Maryland, and colleagues studied a different bacterium, -dweller the ground Clostridium novyi , a relative of the microbe responsible for botulism. Oxygen is the rare tumor inside, and these bacteria "of love of low oxygen zones," said Saurabh Saha, a cancer researcher at BioMed Valley Discoveries Inc. in Kansas City, Missouri, and a co-author of the new study, which appears online today in science Translational Medicine . "They grow and divide and kill cancer cells," says Saha. The researchers speculated that the bacteria release enzymes that destroy tumor cells, and then they feast on the remains.
Inject the spores of the bacteria in brain tumors in rats extended the survival of animals, the researchers found. But the treatments that work in laboratory rodents have a bad habit of not in people, so the researchers wanted to test the bacteria in animals that more closely resemble human patients with cancer. They chose dogs. Like humans, dogs are genetically more diverse than laboratory rodents. And as human tumors, canine tumors grow spontaneously, unlike tumors induced by researcher of laboratory rodents.
Saha and his colleagues injected C. novyi spores in dog tumors 16 animals whose owners have run out of options to treat them. In six dogs, the tumors shrank or disappeared, and tumors stopped growing in five animals. Several dogs needed surgery to erase the injuries that tumors have disintegrated.
Encouraged by the results of animal studies, researchers have begun a trial of treatment with the security people. The first person who received the bacteria was a woman whose abdominal tumor had metastasized to several parts of his body, including his right shoulder. Although the researchers injected within 1% of the bacterial dose dogs had received in the shoulder metastases, growth began to decline. However, treatment stimulated an unusual side effect. The tumor had burst into the humerus bone in the arm, and was apparently provide physical support. Destruction of cancer cells leads to bone breaking, which required surgery to repair. Finally, the patient died of his other metastatic tumors.
The bacteria not only destroy tumor cells, but they also stimulate immune cells to attack the cancer, researchers have shown. And because microbes survive only in low oxygen environment of a tumor, the treatment is specific, said Saha. "It distinguishes tumor from normal cells." The researchers plan to continue their safety trial and want to determine which types of tumors respond to bacterial therapy, he said.
Saha and colleagues altered their bacteria to be less harmful to people and the microbes die when they contact oxygen, limiting their ability to spread. However, some dogs and human patients in the trials received antibiotics, and doctors and other caregivers used anti-infection standard measures such as wearing protective gowns and gloves.
The study is important because it provides "proof of concept that this particular approach can have antitumor activity in" real tumors, "" rather than only in induced tumors of laboratory rodents, said Douglas Thamm, a biologist and cancer researcher in veterinary oncology at the cancer Center Flint animals of the Colorado State University in Fort Collins. doctors may need to combine treatment with other therapies, such as radiation to mop up all tumor cells that escape the bacteria, he said.
"There is a very good very important paper," says biologist cancer Robert Hoffman of AntiCancer Inc., a biotechnology company California based San Diego ,. He and his colleagues have shown that a different strain of Salmonella bacteria than that used in previous clinical trials could eradicate various types of mouse tumors, but they are not carried out studies on human patients .
One concern about the new approach is that most cancer patients are not killed by the original tumor, but metastasis. Thamm and Hoffman fear that the injection C. novyi directly into tumors will leave intact these fatal metastases. "If the bacterial therapy will be widely available and effective," says Hoffman, "it needs to target metastatic disease."
* Correction, August 14, 1445: The researchers genetically modify bacteria to mitigate; they used the heat.
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