iScience (Jun 2020)
A Structurally Simple Vaccine Candidate Reduces Progression and Dissemination of Triple-Negative Breast Cancer
- Amedeo Amedei,
- Fatemeh Asadzadeh,
- Francesco Papi,
- Maria Giuliana Vannucchi,
- Veronica Ferrucci,
- Iris A. Bermejo,
- Marco Fragai,
- Carolina Vieira De Almeida,
- Linda Cerofolini,
- Stefano Giuntini,
- Mauro Bombaci,
- Elisa Pesce,
- Elena Niccolai,
- Francesca Natali,
- Eleonora Guarini,
- Frank Gabel,
- Chiara Traini,
- Stefano Catarinicchia,
- Federica Ricci,
- Lorenzo Orzalesi,
- Francesco Berti,
- Francisco Corzana,
- Massimo Zollo,
- Renata Grifantini,
- Cristina Nativi
Affiliations
- Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 03, 50134 Firenze, Italy
- Fatemeh Asadzadeh
- Department of Molecular Medicine and Medical Biotechnologies, University of Napoli “Federico II”, via Pansini, 5, 80131 Napoli, Italy; CEINGE Biotecnologie Avanzata, Via Gaetano Salvatore 486, 80145 Napoli, Italy
- Francesco Papi
- Department of Chemistry, University of Florence, via della Lastruccia, 3-13, 50019 Sesto Fiorentino (FI), Italy
- Maria Giuliana Vannucchi
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 03, 50134 Firenze, Italy
- Veronica Ferrucci
- Department of Molecular Medicine and Medical Biotechnologies, University of Napoli “Federico II”, via Pansini, 5, 80131 Napoli, Italy; CEINGE Biotecnologie Avanzata, Via Gaetano Salvatore 486, 80145 Napoli, Italy
- Iris A. Bermejo
- Department of Chemistry, University of La Rioja, Madre de Dios, 53, 26006 Logroño, Spain
- Marco Fragai
- Department of Chemistry, University of Florence, via della Lastruccia, 3-13, 50019 Sesto Fiorentino (FI), Italy; CERM, University of Florence, via L. Sacconi, 6, 50019 Sesto Fiorentino (FI), Italy
- Carolina Vieira De Almeida
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 03, 50134 Firenze, Italy
- Linda Cerofolini
- CERM, University of Florence, via L. Sacconi, 6, 50019 Sesto Fiorentino (FI), Italy; Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), via L. Sacconi, 6, 50019 Sesto Fiorentino (FI), Italy
- Stefano Giuntini
- Department of Chemistry, University of Florence, via della Lastruccia, 3-13, 50019 Sesto Fiorentino (FI), Italy; Department of Chemistry, University of La Rioja, Madre de Dios, 53, 26006 Logroño, Spain
- Mauro Bombaci
- Istituto Nazionale Genetica Molecolare, Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Elisa Pesce
- Istituto Nazionale Genetica Molecolare, Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Elena Niccolai
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 03, 50134 Firenze, Italy
- Francesca Natali
- CNR-IOM, c/o Institut Laue-Langevin, 71 avenue des Martyrs, 38000 Grenoble, France
- Eleonora Guarini
- Department of Physics and Astronomy, via Sansone, 1, 50019 Sesto Fiorentino (FI), Italy
- Frank Gabel
- Université Grenobles Alpes, CEA, CNRS, IBS, 38000 Grenoble, France
- Chiara Traini
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 03, 50134 Firenze, Italy
- Stefano Catarinicchia
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 03, 50134 Firenze, Italy
- Federica Ricci
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 03, 50134 Firenze, Italy
- Lorenzo Orzalesi
- Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 03, 50134 Firenze, Italy
- Francesco Berti
- GSK, Thechnical R&D, 53100 Siena, Italy
- Francisco Corzana
- CERM, University of Florence, via L. Sacconi, 6, 50019 Sesto Fiorentino (FI), Italy
- Massimo Zollo
- Department of Molecular Medicine and Medical Biotechnologies, University of Napoli “Federico II”, via Pansini, 5, 80131 Napoli, Italy; CEINGE Biotecnologie Avanzata, Via Gaetano Salvatore 486, 80145 Napoli, Italy; Corresponding author
- Renata Grifantini
- Istituto Nazionale Genetica Molecolare, Padiglione Romeo ed Enrica Invernizzi, IRCCS Ospedale Maggiore Policlinico, Milan, Italy; Corresponding author
- Cristina Nativi
- Department of Chemistry, University of Florence, via della Lastruccia, 3-13, 50019 Sesto Fiorentino (FI), Italy; Corresponding author
- Journal volume & issue
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Vol. 23,
no. 6
p. 101250
Abstract
Summary: 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.
