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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Structure-based Design of Anti-cancer Vaccines: The Significance of Antigen Presentation to Boost the Immune Response

Author(s): Alicia Asín, Fayna García-Martín, Jesús Hector Busto, Alberto Avenoza, Jesús Manuel Peregrina* and Francisco Corzana*

Volume 29, Issue 7, 2022

Published on: 10 August, 2021

Page: [1258 - 1270] Pages: 13

DOI: 10.2174/0929867328666210810152917

Price: $65


Immunotherapy, alone or in combination with other therapies, is widely used against cancer. Glycoprotein Mucin 1 (MUC1), which is overexpressed and aberrantly glycosylated in tumor cells, is one of the most promising candidates to engineer new cancer vaccines. In this context, the development of stable antigens that can elicit a robust immune response is mandatory. Here, we describe the design and in vivo biological evaluation of three vaccine candidates based on MUC1 glycopeptides that comprise unnatural elements in their structure. By placing the Tn antigen (GalNAcα-O-Ser/Thr) at the center of the design, the chemical modifications include changes to the peptide backbone, glycosidic linkage, and carbohydrate level. Significantly, the three vaccines elicit robust immune responses in mice and produce antibodies that can be recognized by several human cancer cells. In all cases, a link was established between the conformational changes induced by the new elements in the antigen presentation and the immune response induced in mice. According to our data, the development of effective MUC1-based vaccines should use surrogates that mimic the conformational space of aberrantly glycosylated MUC1 glycopeptides found in tumors.

Keywords: Cancer vaccine, immunotherapy, mucin, glycopeptide structure, non-natural antigens, tumor-associated carbohydrates, Tn antigen.

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