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A Cancer Therapeutic Vaccine based on Clustered Tn‐Antigen Mimetics Induces Strong Antibody‐Mediated Protective Immunity
Author(s) -
Richichi Barbara,
Thomas Baptiste,
Fiore Michele,
Bosco Rosa,
Qureshi Huma,
Nativi Cristina,
Renaudet Olivier,
BenMohamed Lbachir
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201406897
Subject(s) - immunogenicity , epitope , antigen , antibody , cancer vaccine , immune system , immunology , immunization , antibody titer , immunity , peptide vaccine , cancer , virology , titer , immunotherapy , medicine , biology
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.