Innate immune cell receptors via anti-β-glucan antibody immune complexes

Innate immune cell receptors, primarily Complement Receptor 3 (CR3) and Fc gamma receptor IIa (FcγRIIa), serve as the functional targets for immune complexes formed between soluble beta-glucans and endogenous antibodies (Bose et al., 2016). In the presence of naturally occurring anti-beta-glucan antibodies (ABA), soluble yeast-derived beta-glucans like Imprime PGG (BTH1677) form large immune complexes that activate the classical complement pathway and are opsonized by complement fragments such as iC3b (Bose et al., 2016; US Patent 11815435B2). These opsonized complexes then dual-engage CR3 and FcγRIIa on the surface of innate immune cells, including neutrophils, monocytes, and macrophages, leading to their phenotypic and functional activation (Chan et al., 2019). This activation triggers a cascade of immune responses, including enhanced phagocytosis, reactive oxygen species production, and the secretion of pro-inflammatory cytokines and chemokines, which effectively prime the innate immune system to recognize and kill tumor cells (OncLive, 2020; Chan et al., 2019). The therapeutic utility of this target is highly dependent on the patient's baseline levels of ABA, which serve as a critical predictive biomarker for treatment eligibility and efficacy (Bose et al., 2016). This mechanism is currently being evaluated in clinical trials in combination with checkpoint inhibitors and tumor-targeting antibodies to enhance anti-tumor immunity in various cancers (OncLive, 2020).

Other names

Complement receptor 3CR3Fc gamma receptor IIaFcγRIIaCD11b/CD18CD32Dectin-1CLEC7ABeta-glucan receptorsPGG-glucan receptors

Imprime PGG forms immune complexes with endogenous anti-beta-glucan antibodies, which then dual-engage Complement Receptor 3 (CR3) and Fc gamma receptor IIa (FcγRIIa) on innate immune cells to trigger activation.