Autor: |
Sergey Sennikov, Marina Volynets, Saleh Alrhmoun, Roman Perik-Zavodskii, Olga Perik-Zavodskaia, Marina Fisher, Julia Lopatnikova, Julia Shevchenko, Kirill Nazarov, Julia Philippova, Alaa Alsalloum, Vasily Kurilin, Alexander Silkov |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
|
Zdroj: |
Frontiers in Immunology, Vol 15 (2024) |
Druh dokumentu: |
article |
ISSN: |
1664-3224 |
DOI: |
10.3389/fimmu.2024.1470130 |
Popis: |
IntroductionAdoptive cell therapy using TCR-engineered T-cells is one of the most effective strategies against tumor cells. The TCR T-cell approach has been well tested against a variety of blood neoplasms but is yet to be deeply tested against solid tumors. Among solid tumors, cancer-testis antigens are the most prominent targets for tumor-specific therapy, as they are usually found on cells that lie behind blood-tissue barriers.MethodsWe have employed a novel efficient protocol for MAGE-A3-specific T-cell clonal expansion, performed single-cell multi-omic analysis of the expanded T-cells via BD Rhapsody, engineered a selected T-cell receptor into a lentiviral construct, and tested it in an in vitro LDH-cytotoxicity test.Results and discussionWe have observed a 191-fold increase in the MAGE-A3-specific T-cell abundance, obtained a dominant T-cell receptor via single-cell multi-omic BD Rhapsody data analysis in the TCRscape bioinformatics tool, and observed potent cytotoxicity of the dominant-clonotype transduced TCR T-cells against a MAGE-A3-positive tumor. We have demonstrated the efficiency of our T-cell enrichment protocol in obtaining potent anti-tumor T-cells and their T-cell receptors, especially when paired with the modern single-cell analysis methods. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|