A cancer therapeutic vaccine based on clustered Tn-antigen mimetics induces strong antibody-mediated protective immunity.

ABSTRACT: Tumor-associated carbohydrate antigens (TACAs) are key components of cancer vaccines. A variety of vaccines based on native TACAs such as ?-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.

SUBMITTER: Richichi B 

PROVIDER: S-EPMC4564297 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature