| Autor: |
Rooij, M.A.J. de, Remst, D.F.G., Steen, D.M. van der, Wouters, A.K., Hagedoorn, R.S., Kester, M.G.D., Meeuwsen, M.H., Wachsmann, T.L.A., Ru, A.H. de, Veelen, P.A. van, Verdegaal, E.M.E., Falkenburg, J.H.F., Heemskerk, M.H.M. |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Molecular Therapy-Oncolytics, 28, 1-14. CELL PRESS |
| ISSN: |
2372-7705 |
| Popis: |
To increase the number of cancer patients that can be treated with T cell receptor (TCR) gene therapy, we aimed to identify a set of high-affinity cancer-specific TCRs targeting different melanoma-associated antigens (MAGEs). In this study, pep-tides derived from MAGE genes with tumor-specific expression pattern were identified by human leukocyte antigen (HLA) peptidomics. Next, peptide-HLA tetramers were generated, and used to sort MAGE-specific CD8+ T cell clones from the allogeneic (allo) HLA repertoire of healthy donors. To evaluate the clinical potential, most potent TCRs were sequenced, trans-ferred into peripheral blood-derived CD8+ T cells, and tested for antitumor efficacy. In total we identified, seven MAGE-specific TCRs that effectively target MAGE-A1, MAGE-A3, MAGE-A6, and MAGE-A9 in the context of HLA-A*01:01,-A*02:01, -A*03:01, -B*07:02, -B*35:01, or -C*07:02. TCR gene transfer into CD8' T cells resulted in efficient reactivity against a variety of different tumor types, while no cross-reac-tivity was detected. In addition, major in vivo antitumor effects of MAGE-A1 specific TCR engineered CD8' T cells were observed in the orthotopic xenograft model for established multiple myeloma. The identification of seven MAGE-specific TCRs expands the pool of cancer patients eligible for TCR gene therapy and increases possibilities for personalized TCR gene therapy. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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