The mutation-associated neoantigen functional expansion of specific T cells (MANAFEST) assay: A sensitive platform for monitoring antitumor immunity

Ludmila Danilova, Valsamo Anagnostou, Justina X. Caushi, John William Sidhom, Haidan Guo, Hok Yee Chan, Prerna Suri, Ada Tam, Jiajia Zhang, Margueritta El Asmar, Kristen A. Marrone, Jarushka Naidoo, Julie R. Brahmer, Patrick M. Forde, Alexander S. Baras, Leslie Cope, Victor E. Velculescu, Drew M. Pardoll, Franck Housseau, Kellie N. Smith

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)888-899
Number of pages12
JournalCancer Immunology Research
Volume6
Issue number8
DOIs
StatePublished - Aug 2018

ASJC Scopus subject areas

  • Immunology
  • Cancer Research

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