Salmonella bacteria could offer new hope to pancreatic cancer patients

Researchers at the City of Hope say they have created a therapy to help extend the survival of patients with an aggressive form of pancreatic cancer.

The treatment uses modified salmonella bacteria to target tumors that are highly resistant to other forms of treatment.

"It is a weakened form of the bacteria that would contaminate your spinach," said lead researcher Don Diamond, chair of the Department of Experimental Therapeutics at City of Hope.

This particular form of cancer, known as pancreatic ductal adenocarcinoma, or PDAC, has not shown significant improvement in therapy for more than 25 years, according to the study, which was published online Wednesday in the journal Cancer Immunology Research.

Surgery is rarely successful against PDAC and results in delay, but not a cure, in almost 100 percent of cases, and there's no early warning, Diamond said.

"It's an ugly death," Diamond said. "It's devastating to your loved ones and you're completely helpless, and so the state of affairs are that the best chemo, which is incredibly toxic, buys you six to 10 months of survival — nothing like years. So that's what we are aiming to do - add years to people's lives."

Diamond said he had been personally affected by the disease. His college roommate, a man he had been close to for 33 years, contracted pancreatic cancer in 2010.

"I sort of watched him evaporate, and eventually, of course, he passed away" that same year, Diamond said.

Bacterial-based therapies have been used before, according to the study. For decades they have been used to attack tumors and to treat bladder cancer, often using weakened bacteria as a way to provoke an anti-tumor response at the cancer site.

But, with PDAC, tumor cells have a particularly strong defense against the human body's immune response, according to the study. PDAC tumors secrete a thick barrier that can block drugs from acting on the cells. The cancer cells also produce huge amounts of a molecule that effectively camouflages them from the immune system, so the body can't recognize them to form a response.

In this study, researchers modified salmonella bacteria to carry a piece of DNA that creates molecules that specifically block the cancer cells from creating that camouflage. They then coupled the bacteria with an enzyme that digests the tumor's protective barrier. The enzyme effectively drops the tumor's shield, allowing the bacteria to get in and destroy the cancer cells' immunosuppressive defenses.

The method was applied to different populations of mice in several different tests. In one test, the mice received transplanted pancreatic tumors. The treatment decreased the size of the tumors in all of the animals, and in two-thirds of cases, it resulted in a complete regression, according to the study.

In another test, researchers treated mice that had spontaneously developed the tumors. These animals, left untreated, would normally die within nine or 10 weeks, but to researchers' "shock and surprise" the treatment completely eliminated the tumors, Diamond said. The mice were then able to survive as many as 25 weeks, which "is really almost miraculous," Diamond said.

Researchers are planning to submit the therapy for FDA approval in two years, Diamond said. It could then become available as an experimental treatment.