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

Bioactive Materials 2024年第7期37卷 315-330页

作者： Daping Xie Congwei Han Chonghao Chen Zhencheng Liao senio campos de souza Yiming Niu Joao F.Mano Lei Dong Chunming Wang State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao SARChina State Key Laboratory of Pharmaceutical Biotechnology School of Life SciencesNanjing UniversityNanjing210093China department of Chemistry CICECO-Aveiro Institute of MaterialsUniversity of AveiroCampus Universitario de Santiago3810-193AveiroPortugal National Resource Center for Mutant Mice Nanjing210093China department of Pharmaceutical Sciences Faculty of Health ScienceUniversity of MacaoTaipaMacao SARChina Zhuhai UM Science and Technology Research Institute(ZUMRI) University of MacaoHengqinChina Chemistry and Biomedicine Innovative Center Nanjing UniversityNanjingJiangsu210023China

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“hook”TLR2 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.

关键词： Scaffold vaccine TLR2 agonist Polysaccharide Reactive oxygen species Cross-presentation

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