自噬
交叉展示
透皮
免疫系统
佐剂
抗原
内化
接种疫苗
树突状细胞
免疫疗法
免疫学
医学
抗原呈递
癌症研究
化学
T细胞
药理学
细胞
细胞凋亡
生物化学
作者
Dan Yang,Minglong Chen,Ying Sun,Chaonan Shi,Wenhao Wang,Wanchen Zhao,Ting Wen,Ting Liu,Jintao Fu,Chao Lü,Chuanbin Wu,Guilan Quan,Xin Pan
标识
DOI:10.1016/j.jconrel.2023.04.031
摘要
Despite vaccination having the potency to revolutionize disease treatments, some critical issues including lack of safe and effective delivery system, insufficient internalization and ineffective antigen cross-presentation by dendritic cells (DCs) severely hamper its extensive clinical applications. Herein, we developed a whole cell-encapsulated antitumor vaccine microneedle patch (TCV-DMNs) potentiated with transdermal co-delivery of granulocyte-macrophage colony-stimulating factor (GM-CSF) and autophagy promoter (Tat-beclin 1). After transdermal vaccination with TCV-DMNs, GM-CSF released from DMNs serves as a potent adjuvant to recruit and promote the phagocytosis of antigens by DCs. Subsequently, Tat-beclin 1 promoted DCs maturation and MHC-I-mediated cross-presentation via up-regulated autophagy of DCs. We found that vaccination with TCV-DMNs could not only effectively suppress melanoma challenge, but also lead to regression of established malignancies, followed by a relapse-free survival of >40 days. Collectively, whole cell-encapsulated microneedle-assisted transdermal vaccination TCV-DMNs in combination with autophagy regulation could induce a robust antitumor immune response via enhancing transdermal delivery efficiency, promoting antigen internalization and cross-presentation, together with boosting T cell activities.
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