Cancer
Biothera's Imprime PGG primes the innate immune system to identify and kill cancer cells. The discovery of this entirely new cancer-killing mechanism has the potential to dramatically enhance existing treatments for most major types of cancer. Imprime PGG works with complement-activating, anti-tumor monoclonal antibodies to trigger the body's own immune system to kill cancer cells.
Generally, innate immune cells are not involved in anti-cancer activity because they do not recognize this abnormal human tissue as non-self. Research in multiple cancer models demonstrates that Imprime PGG in combination with monoclonal antibodies or cancer vaccines directs a neutrophil-mediated primary innate immune response against cancer.
Mechanism
Anti-tumor monoclonal antibodies activate a cascade of complement that deposits on the cell surface of a tumor. Complement is a chemotactic agent that attracts immune cells to the site of a challenge. Neutrophils, the most abundant immune cell in the body, bind to the complement on the tumor via Complement Receptor 3 (CR3) but do not attack because they fail to "see" the cancer as non-self.
Imprime PGG binds to a second site on the neutrophil CR3, priming these immune cells for cytotoxic activity. Now when the neutrophils bind to the complement on the tumor, the dually bound CR3 triggers a specific targeted innate immune response that kills the cancer cells.
Preclinical Program
Preclinical studies on the pharmacological effects of Imprime PGG in cancer treatment have been published in peer-reviewd journals. Studies in mice with numerous murine tumor types and various monoclonal antibodies have confirmed anti-tumor activity and assisted in identifying the Imprime PGG's anti-tumor mechanism of action. Xenograft studies in mice implanted with various human tumor lines and treated with Imprime PGG in combination with three different approved human monoclonal antibodies have also demonstrated efficacy and confirmed mechanism of action.
A full series of toxicology studies have been completed with Imprime PGG, which includes single-dose, multiple-dose, reproductive, mutagenicity and immunogenicity/antigenicity studies. No significant adverse events were observed that would cause concern in the continued development of Imprime PGG.
Clinical Program
Biothera plans to initiate a Phase II colon cancer trial in 2007 with Imprime PGG in combination with cetuximab (Erbitux®).