| Autor: |
Marta Ibáñez-Navarro, Adrián Fernández, Adela Escudero, Gloria Esteso, Carmen Campos-Silva, Miguel Ángel Navarro-Aguadero, Alejandra Leivas, Beatriz Ruz Caracuel, Carlos Rodríguez-Antolín, Alejandra Ortiz, Alfonso Navarro-Zapata, Carmen Mestre-Durán, Manuel Izquierdo, María Balaguer-Pérez, Cristina Ferreras, Joaquín Martínez-López, Mar Valés-Gómez, Antonio Pérez-Martínez, Lucía Fernández |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Frontiers in Immunology, Vol 14 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1664-3224 |
| DOI: |
10.3389/fimmu.2023.1187665 |
| Popis: |
IntroductionRefractory/relapsed pediatric acute leukemia are still clinically challenging and new therapeutic strategies are needed. Interactions between Natural Killer Group 2D (NKG2D) receptor, expressed in cytotoxic immune cells, and its ligands (NKG2DL), which are upregulated in leukemic blasts, are important for anti-leukemia immunosurveillance. Nevertheless, leukemia cells may develop immunoescape strategies as NKG2DL shedding and/or downregulation.MethodsIn this report, we analyzed the anti-leukemia activity of NKG2D chimeric antigen receptor (CAR) redirected memory (CD45RA-) T cells in vitro and in a murine model of T-cell acute lymphoblastic leukemia (T-ALL). We also explored in vitro how soluble NKG2DL (sNKG2DL) affected NKG2D-CAR T cells’ cytotoxicity and the impact of NKG2D-CAR T cells on Jurkat cells gene expression and in vivo functionality.ResultsIn vitro, we found NKG2D-CAR T cells targeted leukemia cells and showed resistance to the immunosuppressive effects exerted by sNKG2DL. In vivo, NKG2D-CAR T cells controlled T cell leukemia burden and increased survival of the treated mice but failed to cure the animals. After CAR T cell treatment, Jurkat cells upregulated genes related to proliferation, survival and stemness, and in vivo, they exhibited functional properties of leukemia initiating cells.DiscussionThe data here presented suggest, that, in combination with other therapeutic approaches, NKG2D-CAR T cells could be a novel treatment for pediatric T-ALL. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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