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Fighting Fire With Fire
BNH spoke to David Bermudes, associate director of biology at Vion Pharmaceuticals, about the firm's new TAPET technology, which uses salmonella bacteria to treat cancer patients by inhibiting the growth of tumors.
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Business New Haven
4/19/1999
By: Tammy Rachau
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How are you using the salmonella bacteria to treat cancer?
We've developed strains of salmonella that have a very high degree of attenuation - they have essentially lost the ability to cause disease. What they have is the ability to find their way to tumors when they're administered systemically, by intravenous injection. When they find themselves inside the tumor, they grow to enormous numbers - more than 1,000 times the growth rate of anywhere else in the body - and they suppress tumor growth. It suppresses it by more than 90 percent - but it doesn't cure the cancer. It's not eliminating the tumor, it's just stopping the cancer progression.
How are your strains of salmonella different from the salmonella that causes food poisoning?
One difference is that the bacteria have a mutation in one of the genes for making purines, which are the building blocks for DNA. If you can't make your own purines, you can't make your own DNA, unless you can get purines from somewhere else. In most parts of the body purines are very limiting, but inside of the tumor, purines aren't limiting. So the modified salmonella's growth isn't limited inside of the tumor. Because their ability to grow is limited [outside of the tumor], their ability to cause disease is limited. That's why these genetically engineered salmonella don't cause sickness.
The second kind of modification is that the outer part of the bacteria is a lipid coat, and one part of that coat is a particular lipid molecule [in the unmodified salmonella]. The immune system recognizes that molecule and over-responds. We call that over-response 'septic shock,' which can be lethal. So what we've done is to modify one part of that one molecule, and that almost completely removes the ability to cause septic shock. Now you can have a bacteria that you can administer intravenously, can only grow where it finds purines - which is inside the tumor - and doesn't cause septic shock, so it's safe to administer intravenously.
What kinds of cancers would this
technology by used to treat?
In laboratory mice we've used it to treat melanoma, lung cancer, colon cancer and breast cancer. We have preliminary data that suggests that it probably could be used even more widely. But those cancers I mentioned constitute the major cancers that occur in this country.
How long have you been working on this and at what stage in the development process are you now?
When it began in 1993, this was a collaboration between me, John Pawelek and Brooks Low at Yale. The stage that we're at right now is that we've completed our pre-clinical testing and pre-clinical toxicology, and we've filed with the FDA to begin a clinical trial in humans, [which] we hope to begin this summer.
Where did the idea or the inspiration come from?
It was my idea originally. It came out of the collaboration with John Pawelek and a study that we were doing on the nature of malignant melanoma. It had to do with certain properties of the malignant melanoma - they have certain properties that are similar to white blood cells. So the idea was that there are certain parasites that specialize in attacking the white blood cells. I had the idea: Why don't we try some of those parasites and see if they can also attack cancer cells? We really wound up discovering a number of other things along the way that really got us to the end. But that was the beginning.
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