EAGAN, Minn.--(BUSINESS WIRE)--Biothera’s late stage cancer immunotherapy drug binds to multiple innate immune cell receptors to exert enhanced cytotoxicity against tumor cells. Researchers will present new data showing Imprime PGG® binds to Fc gamma receptors (FcγR) in addition to complement receptor 3 (CR3) on human neutrophils and monocytes at a Keystone Symposia on tumor immunology in Banff, Alberta, Canada.
“Expanding our understanding of the mechanism of action of Imprime PGG may lead to more effective applications of this technology for the benefit of patients,” said Jeremy Graff, Ph.D., Senior Vice President, Biothera Pharmaceutical Research.
Previous in vitro human studies have demonstrated that Imprime PGG forms an immune complex with endogenous anti-beta-glucan antibodies (ABA), immunoglobulin IgG or IgM that are commonly present in human serum, with concentration variations in subjects.
Biothera researchers hypothesized that binding of Imprime PGG – a carbohydrate – would correlate significantly to the IgG2 subclass of the anti-beta-glucan IgG antibodies. As FcγRIIA (CD32A) is the only Fc gamma receptor that has high affinity to the IgG2 subclass, Imprime PGG-ABA immune complex will cross-link CD32A, in addition to CR3. The results corroborated the hypotheses.
“CD32A is an activating Fc gamma receptor that lowers the threshold of immune activation,” said Dr. Graff. “We observed that Imprime PGG engages CD32A, resulting in enhanced functional activity in immune cells, such as increased phagocytosis by macrophages.”
The title of Biothera’s the Keystone Symposia poster (#2019) is, “Imprime PGG, a yeast β-glucan immunomodulator, can engage Fc gamma receptor (FcγR) in addition to complement receptor 3 (CR3) on human neutrophils and monocytes.” The poster presentation is scheduled for 7:30 pm – 10:00 pm on Tuesday, February 10.
Biothera, a privately held U.S. biotechnology company, is developing Imprime PGG, a late clinical stage biologic that modulates the immune response to cancer. Data from the most recent randomized phase 2 study of Imprime PGG in first line non-squamous NSCLC was featured as a late-breaking abstract in the Immunotherapy of Cancer session at ESMO 2014. In this study, which evaluated the addition of Imprime PGG to bevacizumab and carboplatin/paclitaxel versus bevacizumab and chemotherapy alone, objective response rate was 60.4% versus 43.5%, duration of response was 10.3 months versus 5.6 months and median overall survival was 16.1 months versus 11.6 months. Similarly encouraging data have been observed in both squamous and non-squamous subjects in a second randomized Phase 2 study in 1st line NSCLC in combination with cetuximab and in studies in high-risk chronic lymphocytic leukemia and metastatic colorectal cancer. Imprime PGG directly modulates the key effector cells of the innate immune system, neutrophils and monocytes/macrophage, enabling them to recognize and kill antibody-targeted cancer cells. In addition, on-going research points to a secondary, bystander effect of Imprime PGG on both innate and adaptive immune cell types known to exist in the tumor microenvironment, including T-cells, dendritic cells, M-2 macrophages and myeloid derived suppressor cells. Imprime PGG is being evaluated in a phase 3 study in late stage metastatic colorectal cancer and planning is underway for an approvable study in NSCLC.