Cancer treatment

[Guest guest]

> >

> > UPI Science News

> > NEW YORK, Dec. 29 (UPI) -- Gene engineers are waging germ warfare

> > against cancer.

> > By making two genetic alterations, scientists have turned the food

> > poisoning bug Salmonella typhimurium into a potent cancer killer. But

> > the gene altered germs do not harm non-cancerous cells.

> > Mutant salmonella stopped tumors from growing and doubled the

> > survival time of experimental mice in a new study that has given

> > scientists confidence to try the method in humans.

> > Biologist Bermudes says trials of the bacterial cancer therapy

> > in humans could start within three or four months. Melanoma, a deadly

> > skin cancer that strikes more than 41,000 Americans each year, will

most

> > likely be their first target, but Bermudes says the germs may also

> > appear to squelch other major killers, like breast, colon and lung

> > cancer.

> > Bermudes is the associate director of biology at Vion

> > Pharmaceuticals, Inc., the New Haven, Ct.-based biotechnology company

> > developing the technology with collaborators from nearby Yale

University

> > School of Medicine, Texas A & M University, College Station, Texas, and

> > the University of Washington, Seattle.

> > The scientists report their findings in the January issue of the

> > journal Nature Biotechnology.

> > Bermudes says the approach makes use of salmonella's natural

> > preference for cancer cells. Without any gene alterations, he says,

> > salmonella will infect cancer cells at levels about 100 times higher

> > than healthy tissues.

> > He says scientists discovered that bacteria had the potential to

> > combat cancer about two centuries ago, when they observed that tumors

> > would somevimes shrink in patients who had acquired serious infections.

> > They could not make use of this method because the germs attack

> > healthy cells as well as tumors. Now that scientists know how to alter

> > genes, they can remove the lethal traits while holding onto the cancer

> > fighting properties.

> > Starting in about 1993, Bermudes and his team began tinkering with

> > the germ, first removing its ability to make an essential building

block

> > for DNA called purine. Purine dependent salmonella had even a greater

> > hunger for cancer cells, concentrating in tumors at levels that were a

> > thousand times higher than in normal tissues.

> > ``This made it possible to consider salmonella as a therapy, because

> > anti-cancer effects could be seen with injections of small amounts of

> > the germ, not enough to cause dangerous infection,'' he says.

> > But before it could be tried on humans, the scientists had to

> > engineer in a second safety mechanism, to avoid a life-threatening

> > immune response called septic shock.

> > In the new study, the scientists cut out part of the salmonella DNA

> > that produces lipid A, a molecule composed of fats and sugars on the

> > surface of the germs cells.

> > Lipid A provokes the secretion of a substance called tumor necrosis

> > factor-alpha, or TNF-alpha. When the body produces too much TNF-alpha,

> > it can lead to septic shock and ultimately cause organ failure and

> > death.

> > Bermudes says: ``The overreaction of the immune system can be more

> > devastating than the infection itself. That's how your own immune

system

> > can end up doing you in.''

> > By altering lipid A, the scientist created a form of salmonella that

> > will attack cancer, but not hurt the patient.

> > He says, ``It makes the bacteria much safer.''

> > In the current study, the scientists tested the salmonella as a

> > cancer treatment in mice, but also injected the gene altered bacteria

> > into pigs to gauge its safety.

> > Bermudes says that, unlike mice, the immune systems of pigs and

> > humans have strong reactions to lipid A. The genetically modified

> > microbes did not produce septic shock in pigs, he says, which bodes

well

> > for the therapy in humans.

> > Dr. Darveau, of Seattle's University of Washington says,

> > ``What makes it exciting is it's just so novel.''

> > Darveau, who discovered the gene that Bermudes altered to create the

> > cancer-killing mutant, says, however, that it may also be a little

> > scary, ``It scares people, the thought of administering a live

bacteria.

> > ''

> > He says the new technique is potentially very important, because it

> > offers a new approach to treating a disease that kills more than half a

> > million people a year.

> > He says, ``It's a step in the right direction.''

> > (Written by Mara Bovsun in New York)

> >

> >

> >