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标题：A Structurally Simple Vaccine Candidate Reduces Progression and Dissemination of Triple-Negative Breast Cancer
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作者：Amedeo Amedei ; Fatemeh Asadzadeh ; Francesco Papi 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：6
页码：1-53
DOI：10.1016/j.isci.2020.101250
语种：English
出版社：Elsevier
摘要：SummaryThe Tn antigen is a well-known tumor-associated carbohydrate determinant, often incorporated in glycopeptides to develop cancer vaccines. Herein, four copies of a conformationally constrained mimetic of the antigen TnThr (GalNAc-Thr) were conjugated to the adjuvant CRM197, a protein licensed for human use. The resulting vaccine candidate,mime[4]CRMelicited a robust immune response in a triple-negative breast cancer mouse model, correlated with high frequency of CD4+ T cells and low frequency of M2-type macrophages, which reduces tumor progression and lung metastasis growth.Mime[4]CRM-mediated activation of human dendritic cells is reported, and the proliferation ofmime[4]CRM-specific T cells, in cancer tissue and peripheral blood of patients with breast cancer, is demonstrated. The locked conformation of the TnThr mimetic and a proper presentation on the surface of CRM197 may explain the binding of the conjugate to the anti-Tn antibody Tn218 and its efficacy to fight cancer cells in mice.Graphical AbstractDisplay OmittedHighlights•Structurally simple vaccine candidate reduces BC tumor size and delays lung metastasis•TnThr mimetic, fused to CRM197 adjuvant, is able to elicit T and B immune responses•TnThr mimetic-based vaccine candidate able to activate human DCs•The vaccine candidate recruits T helper CD4+ in the tumor microenvironmentMedical Biochemistry; Immunology; Cancer