Liang Jie, Cheng Keman, Li Yao, Xu Jiaqi, Chen Yiwei, Ma Nana, Feng Qingqing, Zhu Fei, Ma Xiaotu, Zhang Tianjiao, Yue Yale, Liu Guangna, Guo Xinjing, Chen Zhiqiang, Wang Xinwei, Zhao Ruifang, Zhao Ying, Shi Jian, Zhao Xiao, Nie Guangjun
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing 100049, China.
Fundam Res. 2021 Dec 22;2(1):23-36. doi: 10.1016/j.fmre.2021.11.032. eCollection 2022 Jan.
Nanocarriers with intrinsic immune adjuvant properties can activate the innate immune system while delivering tumor antigen, thus efficiently facilitating antitumor adaptive immunity. Bacteria-derived outer membrane vesicles (OMVs) are an excellent candidate due to their abundance of pathogen associated molecular patterns. However, during the uptake of OMVs by dendritic cells (DCs), the interaction between lipopolysaccharide and toll-like receptor 4 induces rapid DC maturation and uptake blockage, a phenomenon we refer to as "maturation-induced uptake obstruction" (MUO). Herein we decorated OMV with the DC-targeting αDEC205 antibody (OMV-DEC), which endowed the nanovaccine with an uptake mechanism termed as "not restricted to maturation via antibody modifying" (Normandy), thereby overcoming the MUO phenomenon. We also proved the applicability of this nanovaccine in identifying the human tumor neoantigens through rapid antigen display. In summary, this engineered OMV represents a powerful nanocarrier for personalized cancer vaccines, and this antibody modification strategy provides a reference to remodel the DC uptake pattern in nanocarrier design.
具有内在免疫佐剂特性的纳米载体在递送肿瘤抗原时可激活先天免疫系统，从而有效地促进抗肿瘤适应性免疫。细菌衍生的外膜囊泡（OMV）因其富含病原体相关分子模式而成为极佳的选择。然而，在树突状细胞（DC）摄取OMV的过程中，脂多糖与Toll样受体4之间的相互作用会诱导DC迅速成熟并导致摄取受阻，我们将这种现象称为“成熟诱导摄取阻塞”（MUO）。在此，我们用靶向DC的αDEC205抗体（OMV-DEC）修饰OMV，赋予了这种纳米疫苗一种称为“抗体修饰介导的非成熟限制摄取”（诺曼底）的摄取机制，从而克服了MUO现象。我们还证明了这种纳米疫苗在通过快速抗原展示识别人类肿瘤新抗原方面的适用性。总之，这种工程化的OMV代表了一种用于个性化癌症疫苗的强大纳米载体，这种抗体修饰策略为在纳米载体设计中重塑DC摄取模式提供了参考。
