Liposomal Ag engrafted with peptides of sequence derived from HMGB1 induce potent Ag-specific and anti-tumour immunity.
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.
Faham
Abdus
A
Biochemistry and Molecular Biology, Research School of Biology, ANU College of Medicine, Biology and Environment, The Australian National University, Canberra, ACT, 0200, Australia.
Bennett
David
D
Altin
Joseph G
JG
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood / Q000276:immunology; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D024243:HMGB1 Protein / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008081:Liposomes / Q000276:immunology*; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D024243:HMGB1 Protein; D008081:Liposomes; D007371:Interferon-gamma