EAGAN, MN – August 7, 2006 –A recent discovery, published in the current issue of The Journal of Immunology, further identifies the signaling pathway by which Imprime PGG enables neutrophils (innate immune cells) to recognize and kill complement-coated cancer cells. This research continues to support the use of Imprime PGG as a potential new opportunity in cancer treatment.
Previous studies demonstrated that Imprime PGG, a developmental drug manufactured by Biothera, engages a new arm of the immune system in the fight against cancer. Generally, neutrophils do not recognize cancer cells as non-self, leaving other cells of the immune system to defend the body against cancer. Through a novel mechanism of action, Imprime PGG in combination with complement-activating antibodies engages neutrophils to attack and kill tumor cells.
The new study, “Yeast β-Glucan Amplifies Phagocyte Killing of iC3b-opsonized Tumor Cells via CR3-Syk-PI3-kinase Pathway,” identifies the signaling molecules that trigger tumor cytotoxicity or killing by neutrophils bound with active moiety of Imprime PGG.
“This research furthers our understanding of how Imprime PGG, used in conjunction with anti-tumor monoclonal antibodies, amplifies tumor cell killing,” said Jun Yan, MD, Ph.D., the lead researcher at the Tumor Immunobiology Program at the James Graham Brown Cancer Center, University of Louisville in Louisville, Kentucky. “We believe this may open new opportunities to significantly enhance the efficacy of approved and developmental anti-cancer monoclonal antibodies.”
In a preclinical lymphoma study in mice, the combination of Imprime PGG and monoclonal antibody significantly enhanced tumor regression and survival. Mice treated with the combination therapy achieved a nearly complete cessation of tumor growth, while the tumors of mice treated with monoclonal antibody alone more than tripled in size over time. Similarly, more than 75 percent of combination-treated mice survived 100 days while none of the animals treated with monoclonal antibodies only survived beyond 55 days.
Mechanism of Action
Imprime PGG is a soluble/injectable beta 1,3/1,6 glucan derived from a proprietary strain of yeast (Saccharomyces cerevisiae). In the body, cells called macrophages engulf, digest and break down Imprime PGG into smaller components that subsequently bind to neutrophils, the most abundant immune cell in the body.
The Imprime PGG fragments bind to a receptor on the surface of neutrophils called Complement Receptor 3 (CR3), which primes the neutrophils for cancer cell killing through signaling events involving both SYK and PI 3-kinase. The primed neutrophils are now able to “see” cancer cells targeted with antibodies and complement as non-self, and kill them.
Opportunity for Improved Cancer Therapies
Monoclonal antibodies hold promise for cancer therapy but are not uniformly effective, even in patients whose tumors express a high level of tumor antigen. Developing novel strategies to maximize efficacy of monoclonal antibodies is necessary to overcome this limitation.
Imprime PGG in effect amplifies effectiveness of monoclonal antibodies by engaging additional immune cells to attack tumor cells targeted by antibodies and complement. Based on this mechanism of action, Biothera believes that Imprime PGG will work synergistically with numerous monoclonal antibodies designed to treat a wide range of cancers.
The company has completed a Phase I single-dose, dose-escalation clinical trial with Imprime PGG and has begun a multiple-dose, dose-escalation Phase I study. Biothera plans to initiate a Phase II cancer clinical trial program this year.
About Biothera, the Immune Health Company
Biothera is a biotechnology company dedicated to improving immune health. The company's primary focus is developing pharmaceuticals that engage the innate immune system to fight cancer and that enhance the body’s production of various blood cells following chemotherapy- or radiation-induced myelosuppression. In addition, Biothera manufactures and markets food-grade ingredients that support healthy immune function to the nutritional supplement, functional food, cosmetic and animal nutrition markets.
Biothera, the Immune Health Company