Journal
CANCER IMMUNOLOGY RESEARCH
Volume 6, Issue 8, Pages 888-899Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-18-0129
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Funding
- Lung Cancer Foundation of America/International Association for the Study of Lung Cancer
- NIH [R01 CA203891-01A1]
- Stand Up To Cancer - Cancer Research Institute Cancer Immunology Dream Team Translational Research Grant [SU2C-AACR-DT1012]
- American Association for Cancer Research, the Scientific Partner of SU2C
- Mark Foundation for Cancer Research [MFCR-MIC-001]
- Eastern Cooperative Oncology Group American College of Radiology Imaging Network
- MacMillan Foundation
- U.S. National Institutes of Health [CA121113, CA180950]
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- Commonwealth Foundation
- Bloomberg-Kimmel Institute for Cancer Immunotherapy
- Bloomberg Philanthropies
- NIH Cancer Center Support Grant [P30 CA006973]
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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. (C) 2018 AACR.
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