January 2001

From Yale University

Salmonella in combination with radiation effective against cancer tumors,study by Yale researchers finds

A study of melanoma tumors by Yale researchers shows that Salmonella injections in combination with radiation therapy could provide a promising new cancer therapy.

"Combining radiotherapy with injections of genetically engineered Salmonella provide a new and beneficial treatment for solid tumors," said John Pawelek, senior research scientist in the Department of Dermatology at Yale School of Medicine. "Salmonella is the same bacterium that, in its unaltered or ‘wild type’ form, can cause food poisoning and septic shock."

The study, done in collaboration with Vion Pharmaceuticals, was published in the European Journal of Cancer.

Pawelek, along with David Bermudes, now of Vion, and K. Brooks Low at Yale had previously discovered that Salmonella attacks tumors in mice. In collaboration with Vion Pharmaceuticals, they further developed genetically altered strains of Salmonella that retain the anti-tumor effects, but are non-toxic in rodents, pigs and primates. These findings paved the way for Phase I clinical safety trials in humans, currently underway at three different centers across the United States and one in Europe. This new study suggests that combination therapy with X-rays represents one of the future uses for Salmonella in cancer therapy.

"We were surprised by how effective the combination of Salmonella injections with X-ray treatment was," said Pawelek. "With either X-rays alone or Salmonella alone we could get another two or three weeks of suppression of the tumor growth in mice. But when we combined the two together, we got more than double the effects of the individual treatments. Such a phenomenon is referred to as ‘super additive’. But we still haven’t found a way to completely knock out the tumor. The tumors do come back. What we have done is to remarkably prolong the life of the mice."

Pawelek said the strongest tumor suppression and longest survival of mice were achieved with a single dose of Salmonella and fractional X-ray doses totaling 50Gy (a dosage measurement for X-rays). With this new combination treatment, it took the tumors an average of 100 days longer to reach a size of one gram; this is six times longer than in untreated control mice with Salmonella alone, and about 50 percent longer than with X-rays alone.

"You can go into great detail about why X-rays and Salmonella are so effective together," said Pawelek, "but that is really speculation at this point. We have discovered a novel new therapy, and one of the things we are doing now is to try to understand how it works."

Other Yale researchers on the study included Sara Rockwell, professor of therapeutic radiology and pharmacology and director of Office of Scientific Affairs; Marianne Kelley, research associate in therapeutic radiology at Yale; James Platt, research assistant in dermatology, and Stefano Sodi, research associate in dermatology.












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