Endogenous anti-β-glucan antibodies, a potential predictive biomarker for the efficacy of soluble yeast β-1,3/1,6 glucan (Imprime PGG®) immunotherapy in cancer patients (VAC3P.947)

Abstract

Abstract The innate immune response to Imprime PGG® (Imprime PGG) is being leveraged to develop a novel cancer immunotherapy in conjunction with anti-tumor monoclonal antibodies. Previous research has demonstrated the presence of endogenous anti-β-glucan antibodies (ABA) as a necessary prerequisite for the binding and functional activity of Imprime PGG in innate immune cells. In this study, healthy donors with varying levels of ABA were evaluated to determine the threshold of ABA above which binding and modulation of functions were observed. Donors who had ABA levels above the threshold showed Imprime PGG binding (> 5%) to their neutrophils and monocytes with significant modulation of functions, including, a) activation of complement (C5a), b) increased surface expression of complement receptor 3, c) modulation of activation markers (CD62L), and d) production of selective chemokines (IL-8). The potential of the ABA level being a clinical biomarker was then evaluated in a non-small cell lung cancer trial by segregating patients into biomarker (BM) positive or negative populations based on the established ABA threshold. The BM positive patients showed a significantly increased objective response rate and marked survival benefit not seen in the BM negative patients. These results demonstrate a successful translation of biomarker discovery in healthy donors to clinical utility in cancer patients. ABA is a potential predictive biomarker for efficacy of Imprime PGG immunotherapy.