Dendritic cells that endocytosed antigen-containing IgG-liposomes elicit effective antitumor immunity.
Liposomes represent a promising vehicle to deliver exogenous antigens to dendritic cells (DCs) for tumor immunotherapy. Targeting exogenous antigens to Fcgamma receptors on DCs has been shown to result in efficient presentation of antigen-derived peptides on major histocompatibility complex (MHC) class I and class II molecules. In this study, it was investigated whether DCs that endocytosed physicochemically optimized antigen-containing liposomes conjugated with IgG efficiently present antigens on MHC class I and class II molecules, and consequently induce strong antitumor immune responses. IgG-conjugated liposomes that were 200 nm in diameter without attaching polyethylene glycol were most efficiently endocytosed by DCs. Human monocyte-derived DCs that endocytosed tetanus toxoid (TT)-containing IgG liposomes via CD32 stimulated CD4(+) T cells more strongly than DCs pulsed with TT-containing bare liposomes or with soluble TT. Immunization of mice with DCs that endocytosed ovalbumin (OVA)-containing IgG liposomes but not OVA-containing bare liposomes or soluble OVA completely prevented the growth of OVA-expressing lymphoma cells. Importantly, administration of DCs that endocytosed OVA-containing IgG liposomes to the mice with established OVA-expressing tumors strongly suppressed tumor growth. This study demonstrates an IgG liposome with physicochemical properties suitable for delivering antigens to DCs and paves the way to the application of IgG liposomes for tumor immunotherapy using DCs.
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Kazuko
K
Kawamura
Norimitsu
N
Kadowaki
Ryo
R
Suzuki
Satoshi
S
Udagawa
Satoshi
S
Kasaoka
Naoki
N
Utoguchi
Toshio
T
Kitawaki
Nakaba
N
Sugimoto
Naoki
N
Okada
Kazuo
K
Maruyama
Takashi
T
Uchiyama
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000276:immunology*; D039521:CD11c Antigen / Q000276:immunology; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G; D016219:Immunotherapy, Adoptive; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*
D000951:Antigens, Neoplasm; D039521:CD11c Antigen; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D008081:Liposomes