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Cell-Penetrating Peptide Boosts Cancer Vaccine

Prevents and reduces existing tumors in mice

FRIDAY, Feb. 1, 2002 (HealthDayNews) -- A protein fragment that drags a cancer antigen all the way into an immune system cell could help the body fight off potentially deadly tumors.

A new study says those fragments, called peptides, can help the immune system in mice respond against cancer. They can enable the system's defending troops known as T-cells to get a longer look at the biochemical equivalent of the tumor cell's mug shot, the study says.

The findings appear in the February issue of the journal Nature Biotechnology.

Normally, the body's immune system recognizes its own cells and avoids attacking them. This protective tolerance of familiar cells is usually beneficial, but this system sometimes fails to recognize when "self" cells have become malignant. This poses a problem for researchers trying to develop cancer vaccines that trigger the immune system to fight off a tumor.

Due to this self-tolerance, cells in the immune system are unable to generate a powerful immune response against proteins (antigens) that appear on the surfaces of cancer cells. Researchers have tried to add immune cells called dendritic cells to vaccines to pump up the response, but the effect hasn't consistently worked in clinical tests.

Dr. James Geiger, an assistant professor of surgery at the University of Michigan in Ann Arbor, has studied the use of dendritic cell therapy to attack pediatric tumors.

"One of the issues of dendritic cells is what type of antigen to use, how to get the antigen into the dendritic cells and get it expressed to the T-cells," says Geiger. "There's definitely a ton of issues surrounding that question and how best to optimize that."

Now, researchers at the Baylor College of Medicine believe that adding another type of protein to a cancer vaccine's mix could boost the immune response against tumors.

Lead investigator Rong-Fu Wang and his colleague Helen Wang suspected that cancer cell antigens were not being fully absorbed by the dendritic cells. As a result, the dendritic cells couldn't carry out their function of chopping up the antigen and showing recognizable pieces to the immune system's T cells.

"Those [antigens] will fall off [the dendritic cells' surface] in a very short time," says Rong-Fu Wang. "This leads to the ineffectiveness of a vaccine."

The T-cells, which actually mount the body's immune response, need to "read" the antigens displayed on the surface of dendritic cells in order to track down and attack the cancer.

The solution, suspected Wang, lay in getting the cancer antigens all the way inside the dendritic cells. The researchers bonded cancer antigens to a cell penetrating peptide (CPP), hoping to get the antigens into the dendritic cell and extend the amount of time that the antigen fragments were displayed to the T-cells.

"This [CPP] can carry the cancer peptide into the dendritic cell effectively," says Wang.

The researchers found that -- in a mouse model -- when a CPP was attached to the antigen, dendritic cells stimulated T-cells for at least 24 hours.

Wang found that vaccine-treated mice that were later injected with cancer strain were completed protected from developing the disease.

The researchers then injected mice with a form of melanoma that has proven extremely difficult to treat with cancer immunotherapy, and the tumor was allowed to grow for three days. Upon examination two weeks after the cancer was injected, the researchers found that lung metastasis of the disease was one-quarter of the size in the CPP-vaccinated animals. Animals that received a vaccine without CCP had no such protection.

"We think that we can … eventually achieve complete inhibition of tumor growth in an existing tumor model," says Wang. He is currently developing a similar technique designed to treat human prostate cancer.

Geiger is optimistic about the future potential of dendritic cell vaccines, although he cautions that work remains to be done.

"Like any new therapy, there's going to be a lot of improvements, a lot of modification in the vaccines, says Geiger.

But, he adds, "dendritic cells -- if you look at them from the standpoint of cancer vaccines -- have shown the most promise in animal models and early clinical humans trials of anything that anybody in immunology has seen before."

What To Do

First, check out this immune system primer from The Body.com

Then you can read about cancer vaccines from CancerNews.

SOURCES: Interviews with Rong-Fu Wang, Ph.D., associate professor of immunology, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston; James D. Geiger, M.D., assistant professor, Section of Pediatric Surgery, Department of Surgery, University of Michigan, Ann Arbor; February 2002 Nature Biotechnology
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