STING-activating dendritic cell-targeted nanovaccines that evoke potent antigen cross-presentation for cancer immunotherapy  

作　　者：Nguyen Thi Nguyen Xuan Thien Le Woo Tak Lee Yong Taik Lim Kyung Taek Oh Eun Seong Lee Han-Gon Choi Yu Seok Youn 

机构地区：[1]School of Pharmacy,Sungkyunkwan University,2066 Seobu-ro,Jangan-gu,Suwon,Gyeonggi-do,16419,Republic of Korea [2]Department of Nano Engineering and School of Chemical Engineering,Sungkyunkwan University,2066 Seobu-ro,Jangan-gu,Suwon,Gyeonggi-do,16419,Republic of Korea [3]College of Pharmacy,Chung-Ang University,84 Heukseok-ro,Dongjak-gu,Seoul,06974,Republic of Korea [4]Department of Biotechnology and Department of Biomedical-Chemical Engineering,The Catholic University of Korea,43 Jibong-ro,Bucheon-si,Gyeonggi-do,14662,Republic of Korea [5]College of Pharmacy,Hanyang University,55 Hanyangdaehak-ro,Sangnok-gu,Ansan,15588,Republic of Korea

出　　处：《Bioactive Materials》2024年第12期345-365,共21页生物活性材料（英文）

基　　金：supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT,No.RS-2024-00352440 and No.NRF-2019R1A5A2027340).

摘　　要：Recently,nanovaccine-based immunotherapy has been robustly investigated due to its potential in governing the immune response and generating long-term protective immunity.However,the presentation of a tumor peptide-major histocompatibility complex to T lymphocytes is still a challenge that needs to be addressed for eliciting potent antitumor immunity.Type 1 conventional dendritic cell(cDC1)subset is of particular interest due to its pivotal contribution in the cross-presentation of exogenous antigens to CD8+T cells.Here,the DC-derived nanovaccine(denoted as Si9GM)selectively targets cDC1s with marginal loss of premature antigen release for effective stimulator of interferon genes(STING)-mediated antigen cross-presentation.Bone marrow dendritic cell(BMDC)-derived membranes,conjugated to cDC1-specific antibody(αCLEC9A)and binding to tumor peptide(OVA257-264),are coated onto dendrimer-like polyethylenimine(PEI)-grafted silica nanoparticles.Distinct molecular weight-cargos(αCLEC9A-OVA257-264 conjugates and 2′3′-cGAMP STING agonists)are loaded in hierarchical center-radial pores that enables lysosome escape for potent antigen-cross presentation and activates interferon type I,respectively.Impressively,Si9GM vaccination leads to the upregulation of cytotoxic T cells,a reduction in tumor regulatory T cells(Tregs),M1/M2 macrophage polarization,and immune response that synergizes with αPD-1 immune checkpoint blockade.This nanovaccine fulfills a dual role for both direct T cell activation as an artificial antigen-presenting cell and DC subset maturation,indicating its utility in clinical therapy and precision medicine.

关 键 词：DC-based nanovaccines Artificial antigen-presenting cells Type 1 conventional dendritic cells STING pathway activation Antigen cross-presentation 

分 类 号：R730.51[医药卫生—肿瘤]