Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy

作者：Kaifan Liang, Yinzhe Sun, Laozhi Xie, Yipu Liu, Yang You, Jianpei Xu, Fenfen Ma, Yukun Huang, Qingxiang Song, Wenze Xiao, Jianming Huang, Xiaoling Gao, Jun Chen · 发表于：ACS Nano · 年份：2024 · DOI：10.1021/acsnano.4c01050 · 被引用次数：37 · 研究领域：Extracellular vesicles in disease、RNA Interference and Gene Delivery、Nanoplatforms for cancer theranostics

Tumor cell-derived cancer nanovaccines introduce tumor cell-derived components as functional units that endow the nanovaccine systems with some advantages, especially providing all potential tumor antigens. However, cumbersome assembly steps, potential risks of exogenous adjuvants, as well as insufficient lymph node (LN) targeting and dendritic cell (DC) internalization limit the efficacy and clinical translation of existing tumor cell-derived cancer nanovaccines. Herein, we introduced an endoplasmic reticulum (ER) stress inducer α-mangostin (αM) into tumor cells through poly( d, l -lactide- co -glycolide) nanoparticles and harvested biologically self-assembled tumor cell-derived cancer nanovaccines (αM-Exos) based on the biological process of tumor cell exocytosing nanoparticles through tumor-derived exosomes (TEXs). Besides presenting multiple potential antigens, αM-Exos inherited abundant 70 kDa heat shock proteins (Hsp70s) upregulated by ER stress, which can not only act as endogenous adjuvants but also improve LN targeting and DC internalization. Following subcutaneous injection, αM-Exos efficiently migrated to LNs and was expeditiously endocytosed by DCs, delivering tumor antigens and adjuvants to DCs synchronously, which then powerfully triggered antitumor immune responses and established long-term immune memory. Our study exhibited an all-in-one biologically self-assembled tumor cell-derived cancer nanovaccine platform, and the fully featured cancer nanovaccines assem...