Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma

Lili Ren, Matthias Leisegang, Boya Deng, Tatsuo Matsuda, Kazuma Kiyotani, Taigo Kato, Makiko Harada, Jae Hyun Park, Vassiliki Saloura, Tanguy Lim Seiwert, Everett Vokes, Nishant Agrawal, Yusuke Nakamura

Research output: Contribution to journalArticle

Abstract

To develop a practically applicable method for T-cell receptor (TCR)-engineered T cell immunotherapy targeting neoantigens, we have been attempting to identify neoantigen-specific T cell receptors (TCRs) and establish TCR-engineered T cells in a 3–4-month period. In this study, we report the characterization of T cell repertoires in tumor microenvironment (TME) and identification of neoantigen-specific TCRs after stimulation of patient-derived T cells. We screened 15 potential neoantigen peptides and successfully identified two CD8 + HLA-dextramer + T cells, which recognized MAGOHB G17A and ZCCHC14 P368L . All three dominant TCR clonotypes from MAGOHB G17A -HLA dextramer-sorted CD8 + T cells were also found in T cells in TME, while none of dominant TCR clonotypes from ZCCHC14 P368L -HLA dextramer-sorted CD8 + T cells was found in the corresponding TME. The most dominant TCRA/TCRB pairs for these two neoantigens were cloned into HLA-matched healthy donors’ T lymphocytes to generate TCR-engineered T cells. The functional assay showed MAGOHB G17A TCR-engineered T cells could be significantly activated in a mutation-specific, HLA-restricted and peptide-dose-dependent manner while ZCCHC14 P368L TCR-engineered T cells could not. Our data showed neoantigen-reactive T cell clonotypes that were identified in the patient’s peripheral blood could be present in the corresponding TME and might be good TCRs targeting neoantigens.

Original languageEnglish (US)
Article numbere1568813
JournalOncoImmunology
Volume8
Issue number4
DOIs
StatePublished - Apr 3 2019
Externally publishedYes

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Keywords

  • adoptive T cell therapy
  • cytotoxic T lymphocyte (CTL)
  • engineered T cells
  • Head and neck squamous cell carcinoma (HNSCC)
  • neoantigen
  • T cell receptor (TCR)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Ren, L., Leisegang, M., Deng, B., Matsuda, T., Kiyotani, K., Kato, T., Harada, M., Park, J. H., Saloura, V., Lim Seiwert, T., Vokes, E., Agrawal, N., & Nakamura, Y. (2019). Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma. OncoImmunology, 8(4), [e1568813]. https://doi.org/10.1080/2162402X.2019.1568813