TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against Tumors
Adoptive T-cell therapies tailored for the treatment of solid tumors encounter intricate challenges, necessitating the meticulous selection of specific target antigens and the engineering of highly specific T-cell receptors (TCRs). This study delves into the cytotoxicity and functional characteristi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/10/2805 |
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| author | Alaa Alsalloum Saleh Alrhmoun Julia Shevchenko Marina Fisher Julia Philippova Roman Perik-Zavodskii Olga Perik-Zavodskaia Julia Lopatnikova Vasily Kurilin Marina Volynets Yasushi Akahori Hiroshi Shiku Alexander Silkov Sergey Sennikov |
| author_facet | Alaa Alsalloum Saleh Alrhmoun Julia Shevchenko Marina Fisher Julia Philippova Roman Perik-Zavodskii Olga Perik-Zavodskaia Julia Lopatnikova Vasily Kurilin Marina Volynets Yasushi Akahori Hiroshi Shiku Alexander Silkov Sergey Sennikov |
| author_sort | Alaa Alsalloum |
| collection | DOAJ |
| description | Adoptive T-cell therapies tailored for the treatment of solid tumors encounter intricate challenges, necessitating the meticulous selection of specific target antigens and the engineering of highly specific T-cell receptors (TCRs). This study delves into the cytotoxicity and functional characteristics of in vitro-cultured T-lymphocytes, equipped with a TCR designed to precisely target the cancer-testis antigen NY-ESO-1. Flow cytometry analysis unveiled a notable increase in the population of cells expressing activation markers upon encountering the NY-ESO-1-positive tumor cell line, SK-Mel-37. Employing the NanoString platform, immune transcriptome profiling revealed the upregulation of genes enriched in Gene Ontology Biological Processes associated with the IFN-γ signaling pathway, regulation of T-cell activation, and proliferation. Furthermore, the modified T cells exhibited robust cytotoxicity in an antigen-dependent manner, as confirmed by the LDH assay results. Multiplex immunoassays, including LEGENDplex™, additionally demonstrated the elevated production of cytotoxicity-associated cytokines driven by granzymes and soluble Fas ligand (sFasL). Our findings underscore the specific targeting potential of engineered TCR T cells against NY-ESO-1-positive tumors. Further comprehensive in vivo investigations are essential to thoroughly validate these results and effectively harness the intrinsic potential of genetically engineered T cells for combating cancer. |
| first_indexed | 2024-03-10T21:24:23Z |
| format | Article |
| id | doaj.art-5093cd9ee41b46dc9ecc720514ddf6c1 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T21:24:23Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-5093cd9ee41b46dc9ecc720514ddf6c12023-11-19T15:47:22ZengMDPI AGBiomedicines2227-90592023-10-011110280510.3390/biomedicines11102805TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against TumorsAlaa Alsalloum0Saleh Alrhmoun1Julia Shevchenko2Marina Fisher3Julia Philippova4Roman Perik-Zavodskii5Olga Perik-Zavodskaia6Julia Lopatnikova7Vasily Kurilin8Marina Volynets9Yasushi Akahori10Hiroshi Shiku11Alexander Silkov12Sergey Sennikov13Laboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaDepartment of Personalized Cancer Immunotherapy, Graduate School of Medicine, Mie University, Tsu 514-8507, JapanDepartment of Personalized Cancer Immunotherapy, Graduate School of Medicine, Mie University, Tsu 514-8507, JapanLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaLaboratory of Molecular Immunology, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk 630099, RussiaAdoptive T-cell therapies tailored for the treatment of solid tumors encounter intricate challenges, necessitating the meticulous selection of specific target antigens and the engineering of highly specific T-cell receptors (TCRs). This study delves into the cytotoxicity and functional characteristics of in vitro-cultured T-lymphocytes, equipped with a TCR designed to precisely target the cancer-testis antigen NY-ESO-1. Flow cytometry analysis unveiled a notable increase in the population of cells expressing activation markers upon encountering the NY-ESO-1-positive tumor cell line, SK-Mel-37. Employing the NanoString platform, immune transcriptome profiling revealed the upregulation of genes enriched in Gene Ontology Biological Processes associated with the IFN-γ signaling pathway, regulation of T-cell activation, and proliferation. Furthermore, the modified T cells exhibited robust cytotoxicity in an antigen-dependent manner, as confirmed by the LDH assay results. Multiplex immunoassays, including LEGENDplex™, additionally demonstrated the elevated production of cytotoxicity-associated cytokines driven by granzymes and soluble Fas ligand (sFasL). Our findings underscore the specific targeting potential of engineered TCR T cells against NY-ESO-1-positive tumors. Further comprehensive in vivo investigations are essential to thoroughly validate these results and effectively harness the intrinsic potential of genetically engineered T cells for combating cancer.https://www.mdpi.com/2227-9059/11/10/2805TCRTCR-T cellsNY-ESO-1T-cell activationcellular cytotoxicity |
| spellingShingle | Alaa Alsalloum Saleh Alrhmoun Julia Shevchenko Marina Fisher Julia Philippova Roman Perik-Zavodskii Olga Perik-Zavodskaia Julia Lopatnikova Vasily Kurilin Marina Volynets Yasushi Akahori Hiroshi Shiku Alexander Silkov Sergey Sennikov TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against Tumors Biomedicines TCR TCR-T cells NY-ESO-1 T-cell activation cellular cytotoxicity |
| title | TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against Tumors |
| title_full | TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against Tumors |
| title_fullStr | TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against Tumors |
| title_full_unstemmed | TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against Tumors |
| title_short | TCR-Engineered Lymphocytes Targeting NY-ESO-1: In Vitro Assessment of Cytotoxicity against Tumors |
| title_sort | tcr engineered lymphocytes targeting ny eso 1 in vitro assessment of cytotoxicity against tumors |
| topic | TCR TCR-T cells NY-ESO-1 T-cell activation cellular cytotoxicity |
| url | https://www.mdpi.com/2227-9059/11/10/2805 |
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