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Antigen Chemically Coupled to the Surface of Liposomes Are Cross-Presented to CD8⁺ T Cells and Induce Potent Antitumor Immunity¹

Maiko Taneichi^*, Hideaki Ishida, Kiichi Kajino, Kazumasa Ogasawara, Yuriko Tanaka^*, Michiyuki Kasai^*, Masahito Mori, Mitsuhiro Nishida, Hiroyuki Yamamura, Junichiro Mizuguchi and Tetsuya Uchida^2,*

^* Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan; Department of Pathology, Shiga University of Medical Science, Shiga, Japan; Drug Delivery System Development Division, Nippon Oil and Fat Corporation, Tokyo, Japan; and Department of Immunology, Tokyo Medical University, Tokyo, Japan

We have previously demonstrated that liposomes with differential lipid components display differential adjuvant effects when Ags are chemically coupled to their surfaces. In the present study, Ag presentation of liposome-coupled OVA was investigated in vitro, and it was found that OVA coupled to liposomes made using unsaturated fatty acid was presented to both CD4⁺ and CD8⁺ T cells, whereas OVA coupled to liposomes made using saturated fatty acid was presented only to CD4⁺ T cells. Confocal laser scanning microscopic analysis demonstrated that a portion of the OVA coupled to liposomes made using unsaturated, but not saturated fatty acid, received processing beyond the MHC class II compartment, suggesting that the degradation of OVA might occur in the cytosol, and that the peptides generated in this manner would be presented to CD8⁺ T cells via MHC class I. The ability to induce cross-presentation of an Ag coupled to liposomes consisting of unsaturated fatty acid was further confirmed by in vivo induction of CTL and by the induction of tumor eradication in mice; E.G7 tumors in mice that received combined inoculation with OVA_257–264-liposome conjugates, CpG, and anti-IL-10 mAbs were completely eradicated. In those mice, the frequency of CD8⁺ T cells reactive with OVA_257–264 peptides in the context of H-2K^b was significantly increased. These results suggested that, by choosing lipid components for liposomes, surface-coupled liposomal Ags might be applicable for the development of tumor vaccines to present tumor Ags to APCs and induce antitumor responses.