A Cancer Therapeutic Vaccine based on Clustered Tn‐Antigen Mimetics Induces Strong Antibody‐Mediated Protective Immunity |
| |
| Authors: | Dr. Barbara Richichi Baptiste Thomas Dr. Michele Fiore Dr. Rosa Bosco Dr. Huma Qureshi Prof. Dr. Cristina Nativi Prof. Dr. Olivier Renaudet Dr. Lbachir BenMohamed |
| |
| Affiliation: | 1. Department of Chemistry “Ugo Schiff”, University of Florence via della Lastruccia, 13, 50019 Sesto F.no (FI) (Italy);2. Univ. Grenoble Alpes, DCM, 38000 Grenoble (France);3. CNRS, DCM, 38000 Grenoble (France);4. Laboratory of Celluler and Molecular Immunology, Gavin Herbet Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697 (USA);5. FiorGen, University of Florence via L. Sacconi, 6, 50019 Sesto F.no (FI) (Italy);6. Institut Univ. de France, 103 Bd. Saint Michel, 75005 Paris (France);7. Department of Molecular Biology & Biochemistry and Institute for Immunology, University of California Irvine, School of Medicine, Irvine, CA 92697 (USA) |
| |
| Abstract: | Tumor‐associated carbohydrate antigens (TACAs) are key components of cancer vaccines. A variety of vaccines based on native TACAs such as α‐Tn have shown immunogenicity and protection in preclinical animal studies, however, their weak immunogenicity, low in vivo instability, and poor bioavailability, have discouraged their further evaluations in clinical studies. A new improved vaccine prototype is reported. It is composed of four clustered Tn‐antigen mimetics and a immunogenic peptide epitope that are conjugated to a cyclopeptide carrier. The immunization of mice with this vaccine 1) was safe, 2) induced a strong and long‐lasting Tn‐specific response with IgM/IgG antibodies able to recognize native carbohydrate antigens; 3) produced high titers of IgG1, IgG2a, and IgG3 antibodies; and 4) produced a significant antibody‐dependent regression of tumors and conferred protection. Altogether, these findings pave the way for the clinical development of safe and effective therapeutic vaccines against Tn‐expressing cancers. |
| |
| Keywords: | antitumor agents cancer immunology synthetic vaccines Tn antigen |
|
|
