Abstract B65: Immune cell priming and potentiation of anti-tumor effects by Imprime PGG®

Abstract

Biothera is developing Imprime PGG® (Imprime PGG) for cancer that is synergistic with multiple anti-tumor monoclonal antibodies, demonstrating the potential to improve patient outcomes in a wide range of cancer indications. Although, the antitumor potential of Imprime PGG has now been well documented in several preclinical models, its immunomodulatory potential has not been fully elucidated. Here, we studied the in vivo effects of Imprime PGG, a pharmaceutical grade soluble yeast-derived β-1,3/1,6 glucan, on immune cell binding and function, using both tumor bearing and non-tumor bearing mice. Immunodeficient nude mice, with or without tumor (i.e. MiaPaCa-2 human pancreatic tumor), were administered a single dose of Imprime PGG (i.v.) and 3 days later, immune cells in peripheral blood, spleen, and/or tumor were isolated and evaluated for Imprime PGG binding and function. Using flow cytometric methods, Imprime PGG was found to bind B cells, macrophages, and neutrophils in whole blood and in addition, bound to NK cells in spleen. Notably, in mice bearing tumor, Imprime PGG administration lead to a relatively high percentage of Imprime PGG-bound macrophages and neutrophils in the tumor microenvironment. Furthermore, for the first time, we were able to demonstrate that Imprime PGG administered in vivo had the ability to “prime” immune cells and enhance their antitumor function. Administration of Imprime PGG increased the cytotoxic ability of immune cells, such as macrophages and NK cells, and lead to higher antibody mediated cytotoxicity and increased sensitivity to non-specific stimuli. Likewise, immune cells primed in vivo with Imprime PGG demonstrated increased cytokine responses (such as KC; a mouse isoform of human IL-8, IL-6, G-CSF, and MIP-1α and preliminary cytokine data on tumor infiltrating effector cells support an antitumor profile. Collectively, these results indicate that Imprime PGG when administered in vivo “primes” immune effector cells for enhanced antitumor activity. These observations further validate the potential benefit of combining this unique immunomodulatory drug with antitumor monoclonal antibodies as a positive treatment strategy in cancer.

Citation Format: Yumi Yokoyama, Mariana I. Nelson, Nadine C. Ottoson, Mark N. Kirstein, Richard Walsh, Kyle S. Michel, Michael E. Danielson, Mary A. Antonysamy. Immune cell priming and potentiation of anti-tumor effects by Imprime PGG®. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B65.