The Mutation-Associated Neoantigen Functional Expansion of Specific T Cells (MANAFEST) Assay: A Sensitive Platform for Monitoring Antitumor Immunity.
Cancer Immunol Res
; 6(8): 888-899, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-29895573
ABSTRACT
Mutation-associated neoantigens (MANA) are a target of antitumor T-cell immunity. Sensitive, simple, and standardized assays are needed to assess the repertoire of functional MANA-specific T cells in oncology. Assays analyzing in vitro cytokine production such as ELISpot and intracellular cytokine staining have been useful but have limited sensitivity in assessing tumor-specific T-cell responses and do not analyze antigen-specific T-cell repertoires. The FEST (Functional Expansion of Specific T cells) assay described herein integrates T-cell receptor sequencing of short-term, peptide-stimulated cultures with a bioinformatic platform to identify antigen-specific clonotypic amplifications. This assay can be adapted for all types of antigens, including MANAs via tumor exome-guided prediction of MANAs. Following in vitro identification by the MANAFEST assay, the MANA-specific CDR3 sequence can be used as a molecular barcode to detect and monitor the dynamics of these clonotypes in blood, tumor, and normal tissue of patients receiving immunotherapy. MANAFEST is compatible with high-throughput routine clinical and lab practices. Cancer Immunol Res; 6(8); 888-99. ©2018 AACR.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Monitorização Imunológica
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Linfócitos T CD8-Positivos
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Antígenos de Neoplasias
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Neoplasias
Tipo de estudo:
Diagnostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article