Cancer Research Center uses salmonella to target tumors

CRC Research Director Abraham Eisenstark: “We’ll have a double-whammy. We have the cargo vehicle, the bacteria, and we have the cargo to do some destruction.”
Cancer Research Center scientist Dr. Robert Kazmierczak explains the unique processes of his research on cancer on Friday, Oct. 28, 2016.

Researchers at the Cancer Research Center in Columbia found that a modified strain of salmonella can be used to target and infiltrate cancerous tumors. Abraham Eisenstark, the research director at the CRC, said that the bacteria can be engineered to act as a cargo vehicle and carry cancer-fighting drugs into tumors.

“We’ll have a double-whammy,” Eisenstark said. “We have the cargo vehicle, the bacteria, and we have the cargo to do some destruction.”

Eisenstark said the CRC is now working on loading their strain of salmonella with cancer-fighting cargo. He said a lab in Texas has sent them a snake venom with anti-cancer properties.

“It has other effects, of course,” Eisenstark said. “But we can take the cancer-fighting genes from this venom and put them in the bacteria. Then the bacteria will multiply the venom over and over and over again, inside the tumor.”

Robert Kazmierczak, a researcher at the CRC, said that using salmonella as a vehicle for the drugs could make chemotherapy more effective and cause less severe side effects.

Salmonella-carrying, cancer-fighting drugs would be injected into the bloodstream, Kazmierczak said. Salmonella would circulate through the body and accumulate inside tumors. The bacteria would then multiply, filling the tumor with cancer-fighting drugs.

“You will get the drug concentrated there at the tumor where it will do the most good, where it’s actually supposed to be,” Kazmierczak said.

Because of that concentration, he said, drugs carried by salmonella could kill tumors with a lower dose and would not spread to healthy tissue, reducing many of the side effects of chemotherapy.

The CRC recently sequenced and patented the genome of their salmonella strain. That means they can pick and choose which genes to engineer.

Eisenstark said the CRC’s salmonella strain has two major advantages as a vehicle for cancer-fighting drugs. First, toxic genes that cause the symptoms associated with salmonella infection have been selectively removed from the strain. Second, Eisenstark said researchers at the CRC have engineered the bacteria to feed on the same nutrients as tumors. This makes the bacteria better at targeting cancerous tumors and enables it to starve tumors.

“This takes time, these experiments,” Eisenstark said. “So we are constantly developing the strain.”

The development of the CRC’s strain stretches back over 60 years and across the Atlantic. A Swedish scientist sent an isolated strain of salmonella to the bacteriologist Joshua Lederberg, who passed it along to Milislav Demerec at the Carnegie Institution for Science in New York. As a postdoctoral researcher, Eisenstark worked with Demerec at the institution. He said that organism was the first salmonella genome mapped by scientists.

Eisenstark inherited the collection of salmonella strains from Demerec. In the 1990s, when researchers discovered that salmonella seemed to preferentially accumulate inside tumors, Eisenstark began engineering his strains to be less toxic and better at targeting cancerous tumors.

Kazmierczak took the baton when he joined the CRC in 2006. He took the best strain Eisenstark had developed and continued to engineer it. Last year, Kazmierczak studied the effects of the strain on prostate cancer in mice. He said he wanted to know if the strain was non-toxic and how well it targeted tumors.

Kazmierczak injected mice with the strain one a week for 13 weeks. salmonella in the wild can be deadly to mice, he said, but the CRC’s strain did not appear to affect them. The size of the mice’s tumors shrunk visibly, proving the salmonella had been targeting and starving tumors.

“So I can give this to mice and they’ll run around like nothing is happening while their immune system cleans up the salmonella from non-cancerous cells,” Kazmierczak said. “At the same time, the salmonella will circulate through the mice and actively move toward and invade tumors.”

Eisenstark said the CRC faces one barrier in its research.

“Let’s call it ‘less than optimal funding,’” he said.

There are plenty of potential researchers at MU, Eisenstark said.

“Problem is, they demand salaries,” he added, laughing.

The CRC is a private, nonprofit organization, so that means they rely on donations and federal grants, which are increasingly rare, CRC Director Marnie Clark said.

Eisenstark said his research was fully funded by the National Institute of Health for more than 50 years.

“I never had to worry about money. I just had to take the time to write the proposals,” he said. “That gave us confidence in our research. We knew they would fund our proposals, we just had to do the work.”

For Eisenstark and the CRC, that security is gone, but the work continues.

Edited by Claire Mitzel |

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