Abstract 2834: Identification of a critical level of anti-beta glucan IgG antibody necessary for response to soluble beta-glucan therapy and its application as a biomarker for analysis in clinical trials
Authors: Gorden Keith 
Published: May 2015

Abstract
Soluble beta-glucan is a pathogen associated molecular pattern that can activate the innate immune system and has been shown to enhance anti-tumor antibody function in animal models and human clinical trials. Imprime-PGG is yeast derived soluble beta-glucan that is being developed as an immunotherapuetic drug for administration with approved monoclonal anti-tumor antibodies. We have previously demonstrated that in vitro binding and functional response to Imprime-PGG in whole blood correlates with the level of anti-beta-glucan antibodies (ABA) as determined by ELISA. In donors with high ABA levels, stimulation with Imprime-PGG corresponds with higher levels of complement cascade activation, neutrophil binding, modulation of surface markers and IL-8 production. Additionally we have shown that when intravenous immunoglobulin preparations (IVIG) containing high levels of ABA is added to a whole blood sample, it increases the binding and functional response to Imprime-PGG in vitro. Based on these data, we hypothesized that the level of ABA in patient serum could serve as a potential biomarker predictive of positive clinical outcome. The objective of this study was to determine a range of IgG anti-β glucan at which an individual would be considered to be biomarker positive with regards to being responsive to Imprime-PGG treatment. A panel of 8 donors was selected with low IgG ABA and the levels of ABA were increased by the addition of IVIG to whole blood samples at 2, 5 and 10 mg/mL final concentrations. Significant differences were observed in Imprime-PGG activation with increasing IgG levels in complement cascade activation as measured by C5b-9, neutrophil binding of Imprime-PGG, surface marker modulation and IL-8 expression. Addition of IVIG to 2.5mg/mL showed a difference in complement cascade activation where a level of 5mg/mL was necessary to see a significant difference in the other endpoints measured. Analyzing previous data in healthy donors, this ABA range predicted individuals responsive to Imprime-PGG stimulation. Analysis of clinical trial patient data, segregating individuals into a biomarker positive group based on this range of IgG ABA showed a significant survival benefit over the biomarker negative population. These results confirm that the level of ABA is critical to Imprime-PGG response and provides evidence for an IgG ABA range where response to stimulation occurs that can be used a clinical biomarker. They also provide evidence that in a clinical setting, addition of exogenous ABA could provide a benefit to patients with low ABA levels receiving Imprime-PGG treatment.
Citation Format: Keith Gorden. Identification of a critical level of anti-beta glucan IgG antibody necessary for response to soluble beta-glucan therapy and its application as a biomarker for analysis in clinical trials. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2834. doi:10.1158/1538-7445.AM2014-2834