MUC1 protein overexpressed in human epithelialcarcinoma is a target in development of novel anticancer vaccines.Multiple units of immunodominant B-cell epitope PDTRP MUC1core sequence were conjugated to calix[4,8]arene platformscontaining TLR2 ligand, to produce two novel anticancer self-adjuvant vaccine candidates. The immunogenicity of the syntheticconstructs was investigated by immunization of mice in vivo.ELISA assay evidenced that the vaccine candidates stimulate antiMUC1 IgG antibody production (major for the octavalentconstruct) and no additive e ﬀ ect but a multivalency e ﬀ ect wasobserved when compared to an analogous monovalent. Octa- andtetravalent constructs lacking in PDTRP peptide moieties did notshow anti MUC1 IgG antibody production in mice. The antibodiesinduced by the synthesized constructs are able to recognize the MUC1 structures present on MCF7 tumor cells. The resultsdisplay that calixarenes are convenient platforms for building multicomponent self-adjuvant vaccine constructs promising as immunotherapeutic anticancer agents.
|Titolo:||First Self-Adjuvant Multicomponent Potential Vaccine Candidates by Tethering of Four or Eight MUC1 Antigenic Immunodominant PDTRP Units on a Calixarene Platform: Synthesis and Biological Evaluation|
|Data di pubblicazione:||2013|
|Appare nelle tipologie:||1.1 Articolo in rivista|