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Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4
TCR-like chimeric antigen receptor (CAR-T) cell therapy has emerged as a game-changing strategy in cancer immunotherapy, offering a broad spectrum of potential antigen targets, particularly in solid tumors containing intracellular antigens. In this study, we investigated the cytotoxicity and functio...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606439/ https://www.ncbi.nlm.nih.gov/pubmed/37894816 http://dx.doi.org/10.3390/ijms242015134 |
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author | Alsalloum, Alaa Shevchenko, Julia Fisher, Marina Philippova, Julia Perik-Zavodskii, Roman Perik-Zavodskaia, Olga Alrhmoun, Saleh Lopatnikova, Julia Vasily, Kurilin Volynets, Marina Zavjalov, Evgenii Solovjeva, Olga Akahori, Yasushi Shiku, Hiroshi Silkov, Alexander Sennikov, Sergey |
author_facet | Alsalloum, Alaa Shevchenko, Julia Fisher, Marina Philippova, Julia Perik-Zavodskii, Roman Perik-Zavodskaia, Olga Alrhmoun, Saleh Lopatnikova, Julia Vasily, Kurilin Volynets, Marina Zavjalov, Evgenii Solovjeva, Olga Akahori, Yasushi Shiku, Hiroshi Silkov, Alexander Sennikov, Sergey |
author_sort | Alsalloum, Alaa |
collection | PubMed |
description | TCR-like chimeric antigen receptor (CAR-T) cell therapy has emerged as a game-changing strategy in cancer immunotherapy, offering a broad spectrum of potential antigen targets, particularly in solid tumors containing intracellular antigens. In this study, we investigated the cytotoxicity and functional attributes of in vitro-generated T-lymphocytes, engineered with a TCR-like CAR receptor precisely targeting the cancer testis antigen MAGE-A4. Through viral transduction, T-cells were genetically modified to express the TCR-like CAR receptor and co-cultured with MAGE-A4-expressing tumor cells. Flow cytometry analysis revealed a significant surge in cells expressing activation markers CD69, CD107a, and FasL upon encountering tumor cells, indicating robust T-cell activation and cytotoxicity. Moreover, immune transcriptome profiling unveiled heightened expression of pivotal T-effector genes involved in immune response and cell proliferation regulation. Additionally, multiplex assays also revealed increased cytokine production and cytotoxicity driven by granzymes and soluble Fas ligand (sFasL), suggesting enhanced anti-tumor immune responses. Preliminary in vivo investigations revealed a significant deceleration in tumor growth, highlighting the therapeutic potential of these TCR-like CAR-T cells. Further investigations are warranted to validate these revelations fully and harness the complete potential of TCR-like CAR-T cells in overcoming cancer’s resilient defenses. |
format | Online Article Text |
id | pubmed-10606439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106064392023-10-28 Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4 Alsalloum, Alaa Shevchenko, Julia Fisher, Marina Philippova, Julia Perik-Zavodskii, Roman Perik-Zavodskaia, Olga Alrhmoun, Saleh Lopatnikova, Julia Vasily, Kurilin Volynets, Marina Zavjalov, Evgenii Solovjeva, Olga Akahori, Yasushi Shiku, Hiroshi Silkov, Alexander Sennikov, Sergey Int J Mol Sci Article TCR-like chimeric antigen receptor (CAR-T) cell therapy has emerged as a game-changing strategy in cancer immunotherapy, offering a broad spectrum of potential antigen targets, particularly in solid tumors containing intracellular antigens. In this study, we investigated the cytotoxicity and functional attributes of in vitro-generated T-lymphocytes, engineered with a TCR-like CAR receptor precisely targeting the cancer testis antigen MAGE-A4. Through viral transduction, T-cells were genetically modified to express the TCR-like CAR receptor and co-cultured with MAGE-A4-expressing tumor cells. Flow cytometry analysis revealed a significant surge in cells expressing activation markers CD69, CD107a, and FasL upon encountering tumor cells, indicating robust T-cell activation and cytotoxicity. Moreover, immune transcriptome profiling unveiled heightened expression of pivotal T-effector genes involved in immune response and cell proliferation regulation. Additionally, multiplex assays also revealed increased cytokine production and cytotoxicity driven by granzymes and soluble Fas ligand (sFasL), suggesting enhanced anti-tumor immune responses. Preliminary in vivo investigations revealed a significant deceleration in tumor growth, highlighting the therapeutic potential of these TCR-like CAR-T cells. Further investigations are warranted to validate these revelations fully and harness the complete potential of TCR-like CAR-T cells in overcoming cancer’s resilient defenses. MDPI 2023-10-13 /pmc/articles/PMC10606439/ /pubmed/37894816 http://dx.doi.org/10.3390/ijms242015134 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Alsalloum, Alaa Shevchenko, Julia Fisher, Marina Philippova, Julia Perik-Zavodskii, Roman Perik-Zavodskaia, Olga Alrhmoun, Saleh Lopatnikova, Julia Vasily, Kurilin Volynets, Marina Zavjalov, Evgenii Solovjeva, Olga Akahori, Yasushi Shiku, Hiroshi Silkov, Alexander Sennikov, Sergey Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4 |
title | Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4 |
title_full | Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4 |
title_fullStr | Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4 |
title_full_unstemmed | Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4 |
title_short | Exploring TCR-like CAR-Engineered Lymphocyte Cytotoxicity against MAGE-A4 |
title_sort | exploring tcr-like car-engineered lymphocyte cytotoxicity against mage-a4 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606439/ https://www.ncbi.nlm.nih.gov/pubmed/37894816 http://dx.doi.org/10.3390/ijms242015134 |
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