Potentiation of cancer immunity-inducing effect by pH-sensitive polysaccharide-modified liposomes with combination of TGF-β type I receptor inhibitor-embedded liposomes

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Eiji Yuba Shinya Uesugi Yuta Yoshizaki Atsushi Harada Kenji Kono


Recent success of immune checkpoint inhibitors has revealed that canceling of immunosuppression in tumor microenvironments is crucially important to achieve effective cancer immunotherapy via tumor-specific cytotoxic T lymphocytes (CTLs). Transforming growth factor (TGF)-beta signaling also contributes to immunosuppression in tumors via inactivation of CTL and activation of regulatory T cells. The combination of CTL induction system and blocking system of TGF-beta signaling is attempted in this study using antigen-loaded pH-sensitive polysaccharide-modified liposome and liposome embedded SB505124: an inhibitor of TGF-beta type I receptor. 3-Methylglutarylated dextran (MGlu-Dex)-modified liposomes delivered model antigenic protein, ovalbumin (OVA) into cytosol of dendritic cell line via pH-responsive membrane disruption and subcutaneous administration of these liposomes induced the regression of OVA-expressing tumor in mice. Additional administration of SB505124-embedded liposomes improved antitumor effects and survival in mice. Especially, intravenous administration of SB505124-embedded liposomes promoted the infiltration of CTL to tumor tissues significantly compared with single administration of MGlu-Dex-modified liposomes, leading to strong immunotherapeutic effects. Therefore, the combination of pH-sensitive polysaccharide-modified liposomes and SB-embedded liposomes is promising as an immunity-inducing system for cancer immunotherapy.

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YUBA, Eiji et al. Potentiation of cancer immunity-inducing effect by pH-sensitive polysaccharide-modified liposomes with combination of TGF-β type I receptor inhibitor-embedded liposomes. Medical Research Archives, [S.l.], v. 5, n. 5, may 2017. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/1243>. Date accessed: 21 apr. 2024.
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Research Articles


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