Structure-guided Cancer Vaccines based on Glycopeptides Supported on Diverse Nanoparticles

Cancer is a worldwide problem and various cancer therapies are emerging as potential solutions. Among these cancer therapies, a very attractive strategy is that of therapeutic cancer vaccines, which can use tumor-associated peptide fragments that can induce an immune response. In this thesis, we focus on the peptide sequence of MUC1, a glycoprotein presents on the surface of epithelial cells, which leaves simple carbohydrates, and the backbone of the peptide exposed in cancer cells due to aberrant glycosylation. In nature, this exposure to the immune system doesn't trigger a sufficient immune response, due to elusive mechanisms of the cancer cells. For this reason, the core of the present work is to design MUC1-based peptide vaccines modifying the backbone with non-natural mimetics or using different carrier systems to present the antigen to the immune system. In this thesis are presented two vaccines conjugated that have been shown to elicit high immune response utilizing in one case β-amino acid substitutions in the peptide backbone and utilizing as carrier gold nanoparticles, and a second one utilizing an epitope of the MUC1 along with a T helper epitope conjugated to silica nanoparticles. We also present in this work the synthesis of different MUC1 glycopeptides with modifications in the Arg residue and their comparison in terms of affinity towards the SM3 anti-MUC1 monoclonal antibody to select a vaccine candidate among them.

Grantor dc:publisher

Universidad de La Rioja (España)

Year dc:date

2025

Author dc:creator

• Suárez García, Oscar

Contributors dc:contributor

• Busto Sancirián, Jesús Héctor (Universidad de La Rioja)
• García Martín, Fayna M. (Universidad de La Rioja)

Statement dc:rights

• LICENCIA DE USO: Los documentos a texto completo incluidos en Dialnet son de acceso libre y propiedad de sus autores y/o editores. Por tanto, cualquier acto de reproducción, distribución, comunicación pública y/o transformación total o parcial requiere el consentimiento expreso y escrito de aquéllos. Cualquier enlace al texto completo de estos documentos deberá hacerse a través de la URL oficial de éstos en Dialnet. Más información: https://dialnet.unirioja.es/info/derechosOAI | INTELLECTUAL PROPERTY RIGHTS STATEMENT: Full text documents hosted by Dialnet are protected by copyright and/or related rights. This digital object is accessible without charge, but its use is subject to the licensing conditions set by its authors or editors. Unless expressly stated otherwise in the licensing conditions, you are free to linking, browsing, printing and making a copy for your own personal purposes. All other acts of reproduction and communication to the public are subject to the licensing conditions expressed by editors and authors and require consent from them. Any link to this document should be made using its official URL in Dialnet. More info: https://dialnet.unirioja.es/info/derechosOAI

Language dc:language

eng

Repository record dc:identifier

https://dialnet.unirioja.es/servlet/oaites?codigo=362824

OAI identifier oai:identifier

oai:dialnet.unirioja.es:TES0000023168