Salmonella recruited to fight cancerous tumors

FORT COLLINS, COLO.—Colorado State University (CSU) veterinarians are successfully using genetically modified Salmonella to treat soft-tissue sarcomas and melanoma in pet dogs.

The experimental bacteria thrives in tumors, does not grow in normal tissues and dies if it reaches the environment, says Dr. David Vail, CSU professor of oncology at the Animal Cancer Center.

This form of biologic-based therapy has been tested in the clinical setting for the last five years; and the results are encouraging.

Funded by The Morris Animal Foundation, the researchers believe bacteria have great potential as cancer therapies.

The idea of using bacteria to fight cancer was thought of more than a century ago by Sloan-Kettering practitioner William B. Coley, MD, who noticed some of his cancer patients who developed infections also were having unexpected regressions in their cancer.

"The process is a combination of art and science," Vail says. "The bacteria is made with large pieces of DNA removed, allowing scientists to manipulate it to suit their needs while ensuring it cannot thrive in the environment outside of tumors. The bacteria can be used to elicit an immune response against cancer, or they can be genetically manipulated to produce various anticancer substances once they have invaded the cancer."

In a recently completed Phase-I trial, dogs with cancer presented to Vail's clinic were given a low dose of the treatment, and when it was found to be safe, the dose was gradually increased, Vail says. Now, the known safe dose can be used further in dogs with cancer. The dogs receive the appropriate dose based on number of bacteria and weight of the patient. The treatment is injected intravenously.

Increasing the quality and length of dogs' lives is the goal of the researchers involved, as well as hopes of expanding the treatment to other species if proven successful.

The current treatment protocol

Dogs presenting to the Animal Cancer Center at CSU for treatment of soft-tissue sarcomas whose caregivers opt for this treatment are given an antiemetic and anti-fever drug prior to treatment. Then, an intravenous injection of the bacteria that has been modified to produce a substance that can be seen under the microscope will be given.

Next, the patient will have its tumor surgically removed after the bacterial treatment. The tumor is studied under a microscope to see how well and how long the bacteria infects the tumor as well as other effects.

"In the Phase-I trial, which did not involve surgery, approximately 25 percent of tumors responded, and 10 percent went away completely," Vail says. "Success is measured by the amount the tumor shrinks. It must stop growing for at least six weeks or decrease in size by at least half for a response to be credited to the treatment."

The science must advance further to determine how often the treatment should be given and to determine which types of cancer it might be effective in treating.

"We are years away from having this treatment marketed," Vail adds. "Steps to develop and approve an anti-cancer drug cost approximately $800 million from laboratory to market."

Additional cancer research performed by Vail and CSU colleagues, include development of novel anti-cancer vaccines, anti-cancer drugs, surgical techniques for removing cancerous tumors and methods of improving radiation therapy.

"Cancer in general is the No. 1 cause of diminished life span in dogs," Vail says. "Once a treatment is proven to be safe, it will improve the standard of care veterinarians have to offer across the board."