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...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 cross-presentation.To 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 injection.This vaccine comprises polysaccharide frameworks that“hook”TLR2 agonist(acGM)via tunable hydrophobic interactions and forms a 3D macroporous scaffold via click chemistry upon subcutaneous injection.Its 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 cross-presentation.The 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,respectively.Notably,it requires neither additional adjuvants nor external stimulation to function and can be adjusted to accommodate different antigens.The developed scaffold vaccine may represent a new,competent tool for next-generation personalized cancer vaccination.展开更多
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)+2 种基金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).
文摘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 cross-presentation.To 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 injection.This vaccine comprises polysaccharide frameworks that“hook”TLR2 agonist(acGM)via tunable hydrophobic interactions and forms a 3D macroporous scaffold via click chemistry upon subcutaneous injection.Its 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 cross-presentation.The 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,respectively.Notably,it requires neither additional adjuvants nor external stimulation to function and can be adjusted to accommodate different antigens.The developed scaffold vaccine may represent a new,competent tool for next-generation personalized cancer vaccination.
