Abstract 5627: Antitumor activity of soluble beta-1,3/1,6 glucans: Structure matters
| Autor: | Andy Magee, Carolyn M. Maristany, Faimola Guerrero, Michael E. Danielson, John P. Vasilakos, Richard Walsh, Nandita Bose, Natalie Elmasry, Keith B. Gorden, Anissa S.H. Chan, Lindsay R. Wurst, Will Paul M |
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| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | Cancer Research. 70:5627-5627 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am10-5627 |
| Popis: | Beta-glucan is a pathogen-associated molecular pattern recognized by a variety of innate immune cells. Beta-1,3/1,6 glucans possess numerous immune potentiating activities. In particular, antitumor activity has been demonstrated with the soluble beta glucan Imprime PGG used in combination with complement-activating antitumor monoclonal antibodies (MAb) in several tumor models. Structurally, beta-1,3/1,6 glucans can vary on the basis of chain length, types of linkages, branching, and tertiary structure. Previously, the antitumor activity of soluble beta-1,3/1,6 glucans in combination with antitumor MAb has only been reported using beta glucans derived from yeast. The primary objective of this study was to compare the antitumor activity of three structurally distinct soluble beta-1,3/1,6 glucans in vivo in a mouse syngeneic lymphoma model. Tumor-bearing mice were administered antitumor MAb plus beta glucan 2x/week for 4 weeks. Antitumor activity was based on inhibition of tumor growth at the tumor implantation site and enhanced long-term survival. In addition, critical innate immune cells responsible for antitumor activity were identified focusing on the role of neutrophils. Also, characterization of relevant human immune cells and their beta glucan receptors will be shown focusing on complement receptor 3 (CR3) and dectin-1. Beta glucan binding to immune cells and identification of relevant receptors were determined by flow cytometry using beta glucan-specific antibody and fluorescently-labeled beta glucans. Key findings are that soluble beta glucans, which differ structurally, do not induce similar antitumor activity, and antitumor activity is abrogated in granulocyte-deficient mice. Finally, soluble glucans bind to human neutrophils in a CR3-dependent manner. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5627. |
| Databáze: | OpenAIRE |
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