Oxidized curdlan activates dendritic cells and enhances antitumor immunity

Abstract

Curdlan activates dendritic cells (DCs) and enhances DC-based antitumor immunity. However, hydrophobicity and heterogeneity of curdlan particulates hinder perfect binding of curdlan to dectin-1 receptor, resulting in the reduced activation of antigen presenting cells and limited antitumor effects. Herein, we synthesized partially oxidized curdlan derivative (β-1,3-polyglucuronic acid, denote PGA). PGA-45 polymer, the reaction product prepared from curdlan by oxidation with 4-acetamido-TEMPO/NaClO/NaClO₂ systems under acid conditions for 45 min, activated DCs, induced the expression of co-stimulatory molecules and cytokines, and promoted allogenic T cell proliferation as well as the expression of IL-2. Mechanistically, PGA-45 polymer strongly enhanced phosphorylation of IKK-β and reduced the expression of phosphorylated Akt, suggesting that PGA-45 may activate multiple cell surface receptors such as TLR4 and dectin-1. Administration of tumor lysate pulsed DCs pre-treated with PGA-45 particles induced strong antitumor activity in B16F10 melanoma model. Our data suggest that PGA-45 have strong adjuvant effects for anti-cancer immunity and the design of PGA polymers may provide insights in the development of novel adjuvants for cancer immunotherapy.

Keywords: Cancer immunotherapy; Curdlan; Dectin-1; Dendritic cells; β-1,3-polyglucuronic acid.