A scaffold vaccine to promote tumor antigen cross-presentation via sustained toll-like receptor-2(TLR2)activation

作     者：Daping Xie Congwei Han Chonghao Chen Zhencheng Liao Senio Campos de Souza Yiming Niu Joao F.Mano Lei Dong Chunming Wang 

作者机构：State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoTaipaMacao SARChina State Key Laboratory of Pharmaceutical BiotechnologySchool of Life SciencesNanjing UniversityNanjing210093China Department of ChemistryCICECO-Aveiro Institute of MaterialsUniversity of AveiroCampus Universitario de Santiago3810-193AveiroPortugal National Resource Center for Mutant MiceNanjing210093China Department of Pharmaceutical SciencesFaculty of Health ScienceUniversity of MacaoTaipaMacao SARChina Zhuhai UM Science and Technology Research Institute(ZUMRI)University of MacaoHengqinChina Chemistry and Biomedicine Innovative CenterNanjing UniversityNanjingJiangsu210023China 

出 版 物：《Bioactive Materials》 (生物活性材料（英文）)

年 卷 期：2024年第37卷第7期

页      面：315-330页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the Science and Technology Development Fund,Macao SAR (FDCT,No.0001/2021/AKP,0024/2023/AFJ,0060/2020/AGJ,and 005/2023/SKL) the National Natural Science Foundation of China (NSFC,No.31961160701,32022088,31971309,32001069,32230056,and 32000936) the Natural Science Foundation of Jiangsu Province (BK20200318) the University of Macao (MYRG-GRG2023-00136-ICMS-UMDF and MYRG2022-00100-ICMS) support from the project CICECO-Aveiro Institute of Materials,UIDB/50011/2020,UIDP/50011/2020&LA/P/0006/2020,financed by national funds through the FCT/MEC (PIDDAC) 

主　　题：Scaffold vaccine TLR2 agonist Polysaccharide Reactive oxygen species Cross-presentation 

摘      要：Cancer vaccination holds great promise for cancer treatment,but its effectiveness is hindered by suboptimal activation of CD8+cytotoxic T lymphocytes,which are potent effectors to mediate anti-tumor immune responses.A possible solution is to switch antigen-presenting cells to present tumor antigens via the major histocompatibility complex class I(MHC-I)to CD8+T cells-a process known as *** achieve this goal,we develop a three-dimensional(3D)scaffold vaccine to promote antigen cross-presentation by persisted toll-like receptor-2(TLR2)activation after one *** vaccine comprises polysaccharide frameworks that“hookTLR2 agonist(acGM)via tunable hydrophobic interactions and forms a 3D macroporous scaffold via click chemistry upon subcutaneous *** retention-and-release of acGM enables sustained TLR2 activation in abundantly recruited dendritic cells in situ,inducing intracellular production of reactive oxygen species(ROS)in optimal kinetics that crucially promotes efficient antigen *** scaffold loaded with model antigen ovalbumin(OVA)or tumor specific antigen can generate potent immune responses against lung metastasis in B16-OVA-innoculated wild-type mice or spontaneous colorectal cancer in transgenic ApcMin/+mice,***,it requires neither additional adjuvants nor external stimulation to function and can be adjusted to accommodate different *** developed scaffold vaccine may represent a new,competent tool for next-generation personalized cancer vaccination.