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

  1. García-Martín, Fayna 1
  2. Busto, Jesús Hector 1
  3. Peregrina, Jesús Manuel 1
  4. Avenoza, Alberto 1
  5. Corzana, Francisco 1
  6. Asín, Alicia 1
  1. 1 Departamento de Química. Centro de Investigación en Síntesis Química. Universidad de La Rioja. 26006 Logroño, Spain
Revista:
Current Medicinal Chemistry

ISSN: 0929-8673

Año de publicación: 2022

Volumen: 29

Número: 7

Páginas: 1258-1270

Tipo: Artículo

DOI: 10.2174/0929867328666210810152917 PMID: 34375180 SCOPUS: 2-s2.0-85122711376 WoS: WOS:000767305700008 GOOGLE SCHOLAR

Otras publicaciones en: Current Medicinal Chemistry

Resumen

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 at the 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 stablished 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.