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August 24. 2014 1:32AM

Parasite stimulates immune response to fight cancer


David J. Bzik, PhD, professor of Microbiology and Immunology, Geisel School of Medicine at Dartmouth and Barbara Fox, senior research associate of Microbiology and Immunology. (COURTESY)

A mutant cat parasite may prove to be an effective cancer treatment, according to Dartmouth Researchers.

Known as Toxoplasma gondii (T. gondii), this single-celled parasite is found most often in a cat's intestines but can actually live in any warm blooded animal. Dartmouth Researchers have managed to mutate a strain of T. gondii and found that it reprograms the natural power of the immune system to kill cells.

"We know biologically this parasite has figured out how to stimulate the exact immune responses you want to fight cancer," said David J. Bzik, PhD, professor of microbiology and immunology, Geisel School of Medicine at Dartmouth Hitchcock Medical Center.

For people with compromised immune systems, T. gondii can cause a serious infection if they are unable to fend off the parasite. However, the majority of those infected with T. gondii - about one-third of the world's population and including 60 million Americans - usually show no symptoms, although some can experience a flu-like illness.

That's because a healthy immune system responds vigorously to T. gondii, producing natural killer cells and cytotoxic T cells. This response parallels the way the immune system would attack a tumor since these cell types wage war against cancer cells.

Typically, cancer can shut down the body's defensive mechanisms. But by introducing T. gondii into a tumor environment, it seems to jump start the immune system.

The reason for that, said Barbara Fox, senior research associate of microbiology and immunology at Dartmouth, is because the biology of this parasite is inherently different from strategies that target the immune system.

Fox said those strategies typically, "just tickle immune cells from the outside . But by gaining preferential access to the inside of powerful innate immune cell types, our mutated strain of T. gondii reprograms the natural power of the immune system to clear tumor cells and cancer."

Engineering T. gondii as a cancer vaccine

Now, this does not mean doctors will be injecting cancer patients with live replicating strains of T. gondii, that would be too dangerous. Instead, Bzik and Fox created what they call "cps," which is an immunotherapeutic vaccine.

By deleting a Toxoplasma gene that the parasite needs to make a building block of its genome, the researchers have created a mutant parasite that can be grown in the laboratory but that is unable to reproduce in animals or people.

"Aggressive cancers too often seem like fast moving train wrecks. Cps is the microscopic, but super strong, hero that catches the wayward trains, halts their progression, and shrinks them until they disappear," said Bzik.

The Geisel School of Medicine labs have tested the cps vaccine in aggressive lethal mouse models of melanoma or ovarian cancer and found unprecedented high rates of cancer survival, officials said."Cps stimulates amazingly effective immunotherapy against cancers, superior to anything seen before," said Bzik. "The ability of cps to communicate in different and unique ways with the cancer and special cells of the immune system breaks the control that cancer has leveraged over the immune system."

Translating this to the clinic in the future, Bzik said, the researchers imagine that the vaccine will be administered to cells isolated from the patient.

"Then Trojan Horse cells harboring cps will be given back to the patient as an immunotherapeutic cancer vaccine to generate the ideal immune responses necessary to eradicate their cancer cells and to also provide life-long immunity against any future recurrence of that cancer," Bzik saids.

Though more study is needed before the vaccine is ready for humans, both Fox and Bzik said they believe cancer immunotherapy using cps holds "incredible promise for creating beneficial new cancer treatments and cancer vaccines."

The original proof-of-principle studies for the cps vaccine were funded by a Prouty Pilot Project award.


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