Advances in vaccine development for cancer prevention and treatment in Lynch Syndrome.
Cancer vaccines
Colorectal cancer
Immune prevention
Lynch Syndrome
MMR deficiency
Neoantigens
Journal
Molecular aspects of medicine
ISSN: 1872-9452
Titre abrégé: Mol Aspects Med
Pays: England
ID NLM: 7603128
Informations de publication
Date de publication:
10 2023
10 2023
Historique:
received:
13
04
2023
revised:
06
07
2023
accepted:
12
07
2023
pmc-release:
01
10
2024
medline:
14
8
2023
pubmed:
22
7
2023
entrez:
21
7
2023
Statut:
ppublish
Résumé
Lynch Syndrome (LS) is one of the most common hereditary cancer syndromes, and is caused by mutations in one of the four DNA mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6 and PMS2. Tumors developed by LS carriers display high levels of microsatellite instability, which leads to the accumulation of large numbers of mutations, among which frameshift insertion/deletions (indels) within microsatellite (MS) loci are the most common. As a result, MMR-deficient (MMRd) cells generate increased rates of tumor-specific neoantigens (neoAgs) that can be recognized by the immune system to activate cancer cell killing. In this context, LS is an ideal disease to leverage immune-interception strategies. Therefore, the identification of these neoAgs is an ongoing effort for the development of LS cancer preventive vaccines. In this review, we summarize the computational methods used for in silico neoAg prediction, including their challenges, and the experimental techniques used for in vitro validation of their immunogenicity. In addition, we outline results from past and on-going vaccine clinical trials and highlight avenues for improvement and future directions.
Identifiants
pubmed: 37478804
pii: S0098-2997(23)00044-4
doi: 10.1016/j.mam.2023.101204
pmc: PMC10528439
mid: NIHMS1919231
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
MutL Protein Homolog 1
EC 3.6.1.3
Mismatch Repair Endonuclease PMS2
EC 3.6.1.3
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101204Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA257375
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA217789
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA221707
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA260761
Pays : United States
Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
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