A Structurally Simple Vaccine Candidate Reduces Progression and Dissemination of Triple-Negative Breast Cancer.
Cancer
Immunology
Medical Biochemistry
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
26 Jun 2020
26 Jun 2020
Historique:
received:
23
03
2020
revised:
04
05
2020
accepted:
02
06
2020
entrez:
8
7
2020
pubmed:
8
7
2020
medline:
8
7
2020
Statut:
ppublish
Résumé
The 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]CRM elicited 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 of mime[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.
Identifiants
pubmed: 32629615
pii: S2589-0042(20)30436-3
doi: 10.1016/j.isci.2020.101250
pmc: PMC7322362
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101250Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests F.B. is an employee of the GSK group of companies. All the other authors declare no competing financial interests.
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