Dendritic cell (DC) vaccine immunotherapy applies tumor antigens or tumor cell lysate (TCL)-pulsed DCs to induce an antigen-specific immune response to attack cancer cells. However, tumor antigen alone has limited immunostimulatory effects, and so immunostimulants are needed to prepare mature DCs. In our previous study, curdlan sulfate (CS) showed potent adjuvant properties with the HBV vaccine; therefore, we attempted to use CS to mature TCL-pulsed DCs. We first prepared four CSs (CS1-CS4) with different sulfation (S) degrees and molecular weights (MWs), then studied the structure-activity relationship of CS in vitro and finally screened CS3 (14.316% S content and 30.66 kDa MW) as the DC vaccine adjuvant. An in vivo study showed that a DC vaccine adjuvanted with CS3 significantly prolonged the survival of tumor-bearing mice, reduced tumor burden and inhibited tumor growth. The CS3-adjuvanted DC vaccine increased CD80, MHC-I and MHC-II expression, promoted CD8+ T cell infiltration, upregulated TNF-α and IFN-γ transcription, and downregulated TGF-β transcription in tumor tissues. A preliminary mechanism study showed that CS activated DCs mainly via the TLR4 and TLR2 signalling pathways. Based on these results, we concluded that CS3 is a potential adjuvant for DC vaccines and is worth studying for tumor immunotherapy.
Keywords: Curdlan sulfate; Dendritic cell vaccine; Hepatocellular carcinoma; Structure-activity relationship; TLR2; TLR4.
Copyright © 2019. Published by Elsevier B.V.