Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma
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 charact...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-04-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2019.1568813 |
| _version_ | 1818108915107233792 |
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| author | Lili Ren Matthias Leisegang Boya Deng Tatsuo Matsuda Kazuma Kiyotani Taigo Kato Makiko Harada Jae-Hyun Park Vassiliki Saloura Tanguy Seiwert Everett Vokes Nishant Agrawal Yusuke Nakamura |
| author_facet | Lili Ren Matthias Leisegang Boya Deng Tatsuo Matsuda Kazuma Kiyotani Taigo Kato Makiko Harada Jae-Hyun Park Vassiliki Saloura Tanguy Seiwert Everett Vokes Nishant Agrawal Yusuke Nakamura |
| author_sort | Lili Ren |
| collection | DOAJ |
| description | 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 MAGOHBG17A and ZCCHC14P368L. All three dominant TCR clonotypes from MAGOHBG17A-HLA dextramer-sorted CD8+ T cells were also found in T cells in TME, while none of dominant TCR clonotypes from ZCCHC14P368L-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 MAGOHBG17A TCR-engineered T cells could be significantly activated in a mutation-specific, HLA-restricted and peptide-dose-dependent manner while ZCCHC14P368L 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. |
| first_indexed | 2024-12-11T02:22:56Z |
| format | Article |
| id | doaj.art-15eb1b9017694b209f9bc758b96dd2d5 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-11T02:22:56Z |
| publishDate | 2019-04-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-15eb1b9017694b209f9bc758b96dd2d52022-12-22T01:24:01ZengTaylor & Francis GroupOncoImmunology2162-402X2019-04-018410.1080/2162402X.2019.15688131568813Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinomaLili Ren0Matthias Leisegang1Boya Deng2Tatsuo Matsuda3Kazuma Kiyotani4Taigo Kato5Makiko Harada6Jae-Hyun Park7Vassiliki Saloura8Tanguy Seiwert9Everett Vokes10Nishant Agrawal11Yusuke Nakamura12The University of ChicagoCharité - Universitätsmedizin BerlinThe University of ChicagoThe University of ChicagoJapanese Foundation for Cancer ResearchThe University of ChicagoThe University of ChicagoThe University of ChicagoThe University of ChicagoThe University of ChicagoThe University of ChicagoThe University of ChicagoThe University of ChicagoTo 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 MAGOHBG17A and ZCCHC14P368L. All three dominant TCR clonotypes from MAGOHBG17A-HLA dextramer-sorted CD8+ T cells were also found in T cells in TME, while none of dominant TCR clonotypes from ZCCHC14P368L-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 MAGOHBG17A TCR-engineered T cells could be significantly activated in a mutation-specific, HLA-restricted and peptide-dose-dependent manner while ZCCHC14P368L 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.http://dx.doi.org/10.1080/2162402X.2019.1568813head and neck squamous cell carcinoma (hnscc)t cell receptor (tcr)adoptive t cell therapyneoantigencytotoxic t lymphocyte (ctl)engineered t cells |
| spellingShingle | Lili Ren Matthias Leisegang Boya Deng Tatsuo Matsuda Kazuma Kiyotani Taigo Kato Makiko Harada Jae-Hyun Park Vassiliki Saloura Tanguy Seiwert Everett Vokes Nishant Agrawal Yusuke Nakamura Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma OncoImmunology head and neck squamous cell carcinoma (hnscc) t cell receptor (tcr) adoptive t cell therapy neoantigen cytotoxic t lymphocyte (ctl) engineered t cells |
| title | Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma |
| title_full | Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma |
| title_fullStr | Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma |
| title_full_unstemmed | Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma |
| title_short | Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma |
| title_sort | identification of neoantigen specific t cells and their targets implications for immunotherapy of head and neck squamous cell carcinoma |
| topic | head and neck squamous cell carcinoma (hnscc) t cell receptor (tcr) adoptive t cell therapy neoantigen cytotoxic t lymphocyte (ctl) engineered t cells |
| url | http://dx.doi.org/10.1080/2162402X.2019.1568813 |
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