Recruitment of Innate Immune Cells Provides Additional Killing Mechanism

EAGAN, MINN. – July 15, 2004 – Researchers have identified a natural carbohydrate that recruits innate immune cells to assist monoclonal antibodies in the killing of cancer cells, providing a third mechanism by which this immunotherapy destroys tumors. The results were published in today’s issue of The Journal of Immunology, the official publication of the American Association of Immunologists. An abstract of the article is available at www.jimmunol.org

Monoclonal antibodies, which are manufactured in a lab to target specific antigens present on tumor surfaces, are known to kill cancer cells two ways. One method is to attract Natural Killer and other cells to attack the tumor, a process also known as Antibody-Dependent Cellular Cytotoxicity (ADCC). The other method is to activate the complement system, a series of blood proteins that work together to puncture the tumor cells and destroy them (Complement-Dependent Cytotoxicity or CDC).

A third killing mechanism, discovered by researchers at the James Graham Brown Cancer Center at the University of Louisville, relies on an orally administered yeast beta 1,3/1,6 glucan called WGP^® Beta Glucan. This natural carbohydrate binds to specific receptors on neutrophils, the most abundant immune cell in the body. The binding enables the neutrophils, which are not normally engaged in the fight against cancer, to “see” the cancer as foreign. The antibodies and complement attract the primed neutrophils to the site of the cancer where it joins the attack.

In a recent study, 100 percent of mice with liver cancer that were treated with WGP Beta Glucan three days before the start of monoclonal antibody therapy survived 100 days, compared with only 35 days for mice treated with monoclonal antibodies only. Researchers observed significant increases in tumor regression in mice treated with WGP Beta Glucan in combination with Herceptin^®, a monoclonal antibody developed to treat metastatic breast cancer.

“Our research over the past decade has firmly established the efficacy of beta glucan as an immune system enhancer and more recently as a highly promising complementary cancer immunotherapy,” said Gordon Ross, Ph.D., lead researcher and Director of the Tumor Immunobiology Program at the James Graham Brown Cancer Center. “The next steps will be to study the benefits of WGP Beta Glucan in combination with monoclonal antibodies and cancer vaccines in humans.”

The research provides further evidence of the bioactivity of WGP Beta Glucan, a patented compound owned by Biopolymer Engineering, Inc., a Minnesota biotechnology company that intends to develop it for pharmaceutical use.

Researchers also studied the efficacy of other sources of beta glucan. Treatment combining monoclonal antibodies and barley-based beta glucan resulted in improved long-term survival compared with monoclonal antibody therapy alone. However, the combination of yeast WGP beta glucan and monocloncal antibodies produced significantly better results than did any of the other therapy groups.

Another important finding of the research was the mechanism by which WGP Beta Glucan works to enhance the immune system. Understanding the mechanism of action is a critical step in pharmaceutical development and may enable scientists to further improve the efficacy of WGP Beta Glucan as an immune modulator.

Previous research determined that i.v. soluble beta glucan (NSG^TM from Biopolymer Engineering, Inc.) injected into the body binds directly to certain immune cells, priming them to attack cancer cells. In the new study, Dr. Ross and his colleagues found that orally administered WGP Beta Glucan goes through an intermediate step in which the body breaks down the insoluble glucan into soluble components.

This process was observed using fluorescently labeled WGP Beta Glucan that scientists could track in the animals. The beta glucan was taken up by gastrointestinal macrophages, immune cells that are the body’s first line of defense, and shuttled to reticuloendothelial tissues and bone marrow. Within the marrow, the macrophages degraded the beta glucan and secreted small fragments that bound to specific receptors (CR3) on granulocytes, other type of immune cells including neutrophils and tissue macrophages.

The neutrophils, primed by either i.v. beta glucan or the metabolized oral beta glucan, migrated to the site of tumor cells and killed them. As had been found in earlier research, oral beta glucan-mediated tumor killing also required the presence of complement, a blood protein, on the surface of the cancer cells. Tests in which the tumors lacked complement or the granulocytes lacked CR3, the beta glucan therapy failed.

Biopolymer Engineering, Inc. is a biotechnology company that is pioneering carbohydrate solutions to improve human health. Based in Eagan, Minnesota, the company has more than 40 U.S. patents and patents pending, with additional filings in more than 20 countries that protect its yeast beta glucan products and compounds. Biopolymer Engineering is developing beta glucan applications for pharmaceuticals, nutritional supplements, functional foods, cosmetics and animal feed and nutrition. Website: www.biopolymer.com.

Additional Reading

The following article has more information about the killing mechanism of monoclonal antibodies:

Complement function in mAb-mediated cancer immunotherapy.
Trends Immunol. 2004 Mar;25(3):158-64. Review. No abstract available.
PMID: 15036044 [PubMed - indexed for MEDLINE]


Contact:
David Walsh
Biopolymer Engineering, Inc.
651-256-4606