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., et al.. - In: ISCIENCE. - ISSN 2589-0042. - ELETTRONICO. - 23:(2020), pp. 0-53. [10.1016/j.isci.2020.101250]