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
| Autor: | Angelo Palmigiano, Corrada Geraci, Grazia M. L. Consoli, Pappalardo Ms, Eva Galante, Salvatore D. Di Puma, Angelo Spadaro, Giuseppe Granata |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
PDTRP
medicine.medical_treatment Biomedical Engineering Pharmaceutical Science Bioengineering Peptide Cancer Vaccines Epitope Mice Adjuvants Immunologic MUC1 PDTRP Antigen Cell Line Tumor Neoplasms Elisa Test medicine Animals Humans neoplasms MUC1 Pharmacology chemistry.chemical_classification Mice Inbred BALB C biology Immunodominant Epitopes Immunogenicity self-adjuvant anticancer vaccine Calixarene Mucin-1 Organic Chemistry multivalency Ligand (biochemistry) Virology Toll-Like Receptor 2 self-adjuvant vaccine candidate chemistry Immunoglobulin G Antibody Formation biology.protein Female Calixarenes Antibody Oligopeptides Adjuvant Biotechnology |
| Zdroj: | Bioconjugate chemistry 24 (2013): 1710–1720. doi:10.1021/bc400242y info:cnr-pdr/source/autori:C. Geraci, G. M. L. Consoli, G. Granata, G. Galante, A. Palmigiano, M. Pappalardo, S. D. Di Puma, A. Spadaro/titolo:The 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/doi:10.1021%2Fbc400242y/rivista:Bioconjugate chemistry/anno:2013/pagina_da:1710/pagina_a:1720/intervallo_pagine:1710–1720/volume:24 |
| ISSN: | 1520-4812 1043-1802 |
| DOI: | 10.1021/bc400242y |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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