Abstract
High-mobility group box 1 (HMGB1) protein is a nuclear binding protein which is released by monocytes and macrophages and is a potent maturation signal for dendritic cells (DCs). Synthetic HMGB1-related peptides are reported to be potent DC stimulants. Two HMGB1-related peptides, denoted as pHMGB-89 and pHMGB-106, were explored for their ability to enhance the immunogenicity of Ag-containing liposomes. pHMGB-engrafted liposomes targeted murine CD11c + and CD11b + cells in vitro and in vivo. Vaccination of mice with OVA-containing liposomes engrafted with pHMGB-89 and pHMGB-106 induced OVA-specific T cell priming and production of IgG 1, IgG 2a and IgG 2b antibodies. Importantly, vaccination of mice with B16-OVA-derived plasma membrane vesicles (PMVs) engrafted with pHMGB-89 and pHMGB-106 inhibited tumour growth and metastasis, in syngeneic mice challenged with highly metastatic B16-OVA melanoma. The results show that vaccination with Ag-containing liposomes/PMVs engrafted with HMGB1 peptides could be an effective approach for developing novel vaccines and cancer immunotherapies.
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