| Autor: |
Nadia Mensali, Hakan Köksal, Sandy Joaquina, Patrik Wernhoff, Nicholas P. Casey, Paola Romecin, Carla Panisello, René Rodriguez, Lene Vimeux, Asta Juzeniene, Marit R. Myhre, Anne Fåne, Carolina Castilla Ramírez, Solrun Melkorka Maggadottir, Adil Doganay Duru, Anna-Maria Georgoudaki, Iwona Grad, Andrés Daniel Maturana, Gustav Gaudernack, Gunnar Kvalheim, Angel M. Carcaboso, Enrique de Alava, Emmanuel Donnadieu, Øyvind S. Bruland, Pablo Menendez, Else Marit Inderberg, Sébastien Wälchli |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-39097-x |
| Popis: |
Abstract Osteosarcoma (OS) remains a dismal malignancy in children and young adults, with poor outcome for metastatic and recurrent disease. Immunotherapies in OS are not as promising as in some other cancer types due to intra-tumor heterogeneity and considerable off-target expression of the potentially targetable proteins. Here we show that chimeric antigen receptor (CAR) T cells could successfully target an isoform of alkaline phosphatase, ALPL-1, which is highly and specifically expressed in primary and metastatic OS. The target recognition element of the second-generation CAR construct is based on two antibodies, previously shown to react against OS. T cells transduced with these CAR constructs mediate efficient and effective cytotoxicity against ALPL-positive cells in in vitro settings and in state-of-the-art in vivo orthotopic models of primary and metastatic OS, without unexpected toxicities against hematopoietic stem cells or healthy tissues. In summary, CAR-T cells targeting ALPL-1 show efficiency and specificity in treating OS in preclinical models, paving the path for clinical translation. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full text from SpringerLink