A Synthetic DNA, Multi-Neoantigen Vaccine Drives Predominately MHC Class I CD8+ T-cell Responses, Impacting Tumor Challenge.
Cancer Immunol Res
; 7(2): 174-182, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30679156
ABSTRACT
T-cell recognition of cancer neoantigens is important for effective immune-checkpoint blockade therapy, and an increasing interest exists in developing personalized tumor neoantigen vaccines. Previous studies utilizing RNA and long-peptide neoantigen vaccines in preclinical and early-phase clinical studies have shown immune responses predominantly driven by MHC class II CD4+ T cells. Here, we report on a preclinical study utilizing a DNA vaccine platform to target tumor neoantigens. We showed that optimized strings of tumor neoantigens, when delivered by potent electroporation-mediated DNA delivery, were immunogenic and generated predominantly MHC class I-restricted, CD8+ T-cell responses. High MHC class I affinity was associated specifically with immunogenic CD8+ T-cell epitopes. These DNA neoantigen vaccines induced a therapeutic antitumor response in vivo, and neoantigen-specific T cells expanded from immunized mice directly killed tumor cells ex vivo These data illustrate a unique advantage of this DNA platform to drive CD8+ T-cell immunity for neoantigen immunotherapy.
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Base de dados:
MEDLINE
Assunto principal:
Antígenos de Histocompatibilidade Classe I
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Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
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Vacinas Anticâncer
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Vacinas de DNA
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Antígenos de Neoplasias
Limite:
Animals
Idioma:
En
Revista:
Cancer Immunol Res
Ano de publicação:
2019
Tipo de documento:
Article