Noncoding regions are the main source of targetable tumor-specific antigens.
Sci Transl Med
; 10(470)2018 12 05.
Article
em En
| MEDLINE
| ID: mdl-30518613
ABSTRACT
Tumor-specific antigens (TSAs) represent ideal targets for cancer immunotherapy, but few have been identified thus far. We therefore developed a proteogenomic approach to enable the high-throughput discovery of TSAs coded by potentially all genomic regions. In two murine cancer cell lines and seven human primary tumors, we identified a total of 40 TSAs, about 90% of which derived from allegedly noncoding regions and would have been missed by standard exome-based approaches. Moreover, most of these TSAs derived from nonmutated yet aberrantly expressed transcripts (such as endogenous retroelements) that could be shared by multiple tumor types. Last, we demonstrated that, in mice, the strength of antitumor responses after TSA vaccination was influenced by two parameters that can be estimated in humans and could serve for TSA prioritization in clinical studies TSA expression and the frequency of TSA-responsive T cells in the preimmune repertoire. In conclusion, the strategy reported herein could considerably facilitate the identification and prioritization of actionable human TSAs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA Intergênico
/
Antígenos de Neoplasias
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Neoplasias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Transl Med
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Canadá