August 8, 2008

Researchers Using Bacteria to Help Fight Cancer

While most of the country is trying to avoid salmonella by not eating jalapeno peppers, Neil Forbes is embracing the bacteria to help fight a deadly disease: cancer.

Forbes, an assistant professor of chemical engineering at the University of Massachusetts, Amherst, is arming the toxin to burrow itself into tumors and eat cancer cells. A few other researchers are using powerful bacteria such as salmonella to target tumors.

Unlike the strain of salmonella that has sickened more than 1,200 people in recent months, the genetically engineered salmonella that Forbes uses can be cleared by the body's immune system before symptoms arise.

His work, and others like it, highlights the intense search for treatments that target cancer cells without causing debilitating side effects such as weight and hair loss that are common with radiation and chemotherapy.

Salmonella, a type of bacteria, naturally accumulate around tumors because bacteria like to eat, and tumors are a great source of food. Forbes, using a $1 million grant from the National Institutes of Health, has found a way to drive the salmonella, which swim like sperm, into a section of tumors where chemotherapy is generally ineffective.

Studies in mice show the treatment has potential. All mice with tumors that received saline solution were dead after 30 days. Those receiving salmonella and zaps of radiation were alive after 30 days. None got sick from the toxin.

Studies to be published in the next few months in a leading cancer journal will show that Forbes's salmonella, zapped with a low dose of radiation, do a better job of shrinking tumors in mice than does radiation therapy alone.

Forbes said his research doesn't represent a cure , though several cancer patients contacted him about human trials .

"I think there's a lot of desire with cancer patients who have reached the end and want to try something new," Forbes said.

Chemo and radiation do a good job of eliminating cancer cells but kill healthy cells, too .

It can be challenging for therapy to kill nondividing cells sometimes referred to as quiescent cells. When these cells are left to live, tumors may continue to grow. Forbes has engineered his salmonella to create a cancer-cell killing protein and burrow in the region where quiescent cells live, a promising starting point for eliminating tumors when combined with radiation treatment.

"Instead of fighting it like a one-sided front, you're actually fighting them on both sides."

Researchers have moved toward finding specific therapies rather than relying on just chemo and radiation, said Dr. Len Lichtenfeld, deputy chief medical officer at the American Cancer Society. He compared the difference between targeted therapy and chemo to the difference between "a cannon and a rifle shot."

Novartis AG's Gleevec is a targeted therapy, Lichtenfeld said. Gleevec was approved by the U.S. Food and Drug Administration in 2003 to treat chronic myelogenous leukemia, which can lead to anemia, easy bleeding and strokes.

Before the treatment , the lifespan for people with this type of leukemia was four to five years. But now people taking the drug can live for years with the disease, Lichtenfeld said.

Forbes hasn't studied his research in humans but says such studies are on the radar. He said he is trying to perfect the process for steering the salmonella into the tumors and wants to get to the point where he can use minimal radiation in tandem with it. He faces an uphill battle, researchers say.

"The big problem is when he gets to humans, but that shouldn't deter him," said Dr. John Pawelek, a senior research scientist at Yale's School of Medicine.

He would know. Pawelek and a few other s created the nontoxic salmonella that Forbes has replicated for his research, and tried bringing it to market .

Pawelek said research in mice, where "salmonella attacked the tumors with a vengeance," didn't translate well into humans. He said the trials used a weaker form of salmonella because they were concerned about having any of the cancer patients, whose immune systems are already weakened, die during clinical trials.

No patients died from the toxin.

Results published in the Journal of Clinical Oncology in 2002 said the treatment did not have anti-tumor effects in humans. The article noted more studies were needed .

Pawelek said Forbes's research appears promising because he is using salmonella armed with the ability to create a protein that kills cancer cells.

study details

Researcher Neil Forbes is using salmonella to attack cancer cells in mice.

Salmonella accumulate around tumors because bacteria like to eat, and tumors are a great source of food.

Forbes has found a way to drive the salmonella, which swim like sperm, into a section of tumors where chemotherapy is generally ineffective. AT RIGHT: Inside the heart is a magnified picture of a salmonella bacterium.