Cancer therapy using bacteria shows promise in Hopkins tests

Combined with drug, treatment destroys tumors in 75% of mice

November 27, 2001|By Jonathan Bor | Jonathan Bor,SUN STAFF

Cancer researchers at the Johns Hopkins University are reporting today that they have destroyed tumors in mice with a therapeutic cocktail that includes a dose of cancer-eating bacteria.

Dr. Bert Vogelstein, whose lab at Hopkins' Comprehensive Cancer Center has produced some of the key understandings in cancer genetics, said the treatment delivered a one-two punch that cured 75 percent of the mice that received it.

A single injection of bacteria that thrive only in oxygen-starved environments devoured the growths from the inside out. Meanwhile, a chemotherapy drug attacked the remaining tissue on the tumors' outer rim.

Within a day of treatment, the tumors turned into a blackened mass of dead tissue that resembled a scab. Within a few weeks, the tissue was absorbed by the body -- leaving no viable cancer and hardly a trace that it ever existed.

"I never expected to see all the tumor cells die like this," said Vogelstein. "This is certainly the most promising therapeutic development that's happened in our lab."

Vogelstein cautioned that the treatment is several years away from being tested on humans. First, it must prove a success in a wider variety of animals and tumor types, and its side-effects must be reduced.

In the experiment described in today's edition of the journal Proceedings of the National Academy of Sciences, the treatment was tried on hundreds of mice that had large tumors produced by human colon cancer cells.

The findings

Though 75 percent of the mice were cured of their cancers, about 15 percent died within a few days of treatment.

Why they died remains unclear, but Vogelstein said the mice apparently succumbed to toxins that are released when tumors die very quickly. The effect, called tumor lysis syndrome, has been observed in some cancer therapies used on humans and is often counteracted with drugs, he said.

In about 10 percent of the mice, tumors grew back a few weeks after treatment, though Vogelstein said some of these growths responded completely when the animals were treated a second time.

Excitement and caution

Outside Hopkins, cancer researchers who had read advance copies of the article viewed the research with excitement and caution.

"It's a wonderfully clever idea and certainly deserves the chance to prove itself in patients with cancer," said Dr. Sanford Markowitz, a professor of cancer genetics at Case Western Reserve University in Cleveland.

Adding that it will first have to cross safety hurdles in animals, he said, "You keep your fingers crossed, light candles, say prayers and hope it will make the leap into human patients."

Dr. Jorge Gomez, chief of the organ systems branch of the National Cancer Institute, said the therapy might become an important element in a multipronged attack. From early evidence, he said, it appears to address an aspect of cancer -- the poorly oxygenated portion of tumors -- that has resisted conventional treatments.

"What they are using here are bacteria that are very happy in that environment," Gomez said.

Vogelstein said he does not expect the therapy to replace surgery, which remains the best way of removing early cancers. But he said it might someday prove an important adjunct to other approaches -- including radiation and chemotherapy -- that are used on more advanced cancers.

Not a new idea

The idea of using bacteria to digest and destroy tumors is not entirely new, said Vogelstein.

German scientists, using various bacterial strains, tried it unsuccessfully about 50 years ago. The bacteria took root in the tumors but did little to vanquish the cancer, he said.

"It's something we had been thinking about a long time," said Vogelstein, adding that research was started more than a year ago by Long H. Dang, a post-doctoral fellow. Other scientists involved in the research were Chetan Bettegowda, David L. Huso and Kenneth Kinzler.

The work began at a time when scientists across the country were eagerly pursuing the opposite tactic: choking tumors with drugs that inhibit blood vessels that supply nourishing oxygen.

The problem with that approach, said Vogelstein, is that tumors eventually outgrow their blood supply. They can thrive even when portions of them die from little or no blood supply.

For Vogelstein, those oxygen-starved tumor cells presented another target for anti-cancer therapy. Trying 26 species of bacteria that grow only in an oxygen-depleted environment, he found one that not only grew in a tumor's dead zone but rapidly devoured it.

The bacteria, called clostridium novyi, live widely in soil and dust but do not cause disease in animals or humans, Vogelstein said.

Applying them to cancerous mice, he found that the bacteria destroyed the tumors but also released a lethal toxin. Later, the Hopkins scientists engineered a new strain of the bacteria that lacked the toxin-producing gene, making the bacteria safe.

Attacking inside, outside

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