A Structurally Simple Vaccine Candidate Reduces Progression and Dissemination of Triple-Negative Breast Cancer

Amedei, A.; Asadzadeh, F.; Papi, F.; Vannucchi, M. G.; Ferrucci, V.; Bermejo, I. A.; Fragai, M.; De Almeida, C. V.; Cerofolini, L.; Giuntini, S.; Bombaci, M.; Pesce, E.; Niccolai, E.; Natali, F.; Guarini, E.; Gabel, F.; Traini, C.; Catarinicchia, S.; Ricci, F.; Orzalesi, L.; Berti, F.; Corzana, F.; Zollo, M.; Grifantini, R.; Nativi, C.

doi:10.1016/j.isci.2020.101250

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.

A Structurally Simple Vaccine Candidate Reduces Progression and Dissemination of Triple-Negative Breast Cancer / Amedei A.; Asadzadeh F.; Papi F.; Vannucchi M.G.; Ferrucci V.; Bermejo I.A.; Fragai M.; De Almeida C.V.; Cerofolini L.; Giuntini S.; Bombaci M.; Pesce E.; Niccolai E.; Natali F.; Guarini E.; Gabel F.; Traini C.; Catarinicchia S.; Ricci F.; Orzalesi L.; Berti F.; Corzana F.; Zollo M.; Grifantini R.; Nativi C.. - In: ISCIENCE. - ISSN 2589-0042. - ELETTRONICO. - 23:(2020), pp. 0-53. [10.1016/j.isci.2020.101250]