Personalized cancer vaccines from bacteria-derived outer membrane vesicles with antibody-mediated persistent uptake by dendritic cells  

作　　者：Jie Liang Keman Cheng Yao Li Jiaqi Xu Yiwei Chen Nana Ma Qingqing Feng Fei Zhu Xiaotu Ma Tianjiao Zhang Yale Yue Guangna Liu Xinjing Guo Zhiqiang Chen Xinwei Wang Ruifang Zhao Ying Zhao Jian Shi Xiao Zhao Guangjun Nie 

机构地区：[1]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 [2]Center of Materials Science and Optoelectronics Engineering,University of Chinese Academy of Sciences,Beijing 100049,China [3]IGDB-NCNST Joint Research Center,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China

出　　处：《Fundamental Research》2022年第1期23-36,共14页自然科学基础研究（英文版）

基　　金：the National Key R&D Program of China(Grants No.2018YFA0208900,2018YFE0205300,and 2021YFA0909900);the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB36000000);the CAS Project for Young Scientists in Basic Research(Grant No.YSBR-010);the Beijing Natural Science Foundation of China(Grant No.Z200020);the Beijing Nova Program(Z201100006820031);the National Natural Science Foundation of China(Grants No.32171384,31800838,31820103004,31730032,and 51861145302);the Key Research Project of Frontier Science of the Chinese Academy of Sciences(Grant No.QYZDJ-SSW-SLH022);the Innovation Research Group of National Natural Science Foundation(Grant No.11621505).

摘　　要：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 aDEC205 antibody(OMV-DEC),which endowed the nanovaccine with an uptake mechanism termed as 4<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.

关 键 词：Tumor vaccine Outer membrane vesicles Antibody modification Antigen display Dendritic cell uptake Myeloid derived suppressor cells 

分 类 号：R730[医药卫生—肿瘤] R186[医药卫生—临床医学]