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

Article


Geraci, Corrada, Consoli, Grazia M. L., Granata, Giuseppe, Galante, E., Palmigiano, Angelo, Pappalardo, Maria, Di Puma, Salvatore D. and Spadaro, Angelo 2013. 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. Bioconjugate Chemistry. 24 (10), pp. 1710-1720.
AuthorsGeraci, Corrada, Consoli, Grazia M. L., Granata, Giuseppe, Galante, E., Palmigiano, Angelo, Pappalardo, Maria, Di Puma, Salvatore D. and Spadaro, Angelo
Abstract

MUC1 protein overexpressed in human epithelial carcinoma is a target in development of novel anticancer vaccines. Multiple units of immunodominant B-cell epitope PDTRP MUC1 core sequence were conjugated to calix[4,8]arene platforms containing TLR2 ligand, to produce two novel anticancer self-adjuvant vaccine candidates. The immunogenicity of the synthetic constructs was investigated by immunization of mice in vivo. ELISA assay evidenced that the vaccine candidates stimulate anti MUC1 IgG antibody production (major for the octavalent construct) and no additive effect but a multivalency effect was observed when compared to an analogous monovalent. Octa- and tetravalent constructs lacking in PDTRP peptide moieties did not show anti MUC1 IgG antibody production in mice. The antibodies induced by the synthesized constructs are able to recognize the MUC1 structures present on MCF7 tumor cells. The results display that calixarenes are convenient platforms for building multicomponent self-adjuvant vaccine constructs promising as immunotherapeutic anticancer agents.

JournalBioconjugate Chemistry
Journal citation24 (10), pp. 1710-1720
ISSN1043-1802
Year2013
PublisherAmerican Chemical Society
Digital Object Identifier (DOI)doi:10.1021/bc400242y
Web address (URL)https://doi.org/10.1021/bc400242y
Publication dates
Online22 Aug 2013
Publication process dates
Deposited18 Aug 2017
Accepted01 Aug 2013
Copyright information© The American Chemical Society 2013
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