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Updated: Oct 11, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Pre-clinical validation of OSCAR-3 mRNA-based CAR T cells for targeting osteosarcomas
Nadia Mensali1, Sandy Joaquina1, Constance de Montlaur2
1Translational Research Unit, Section of Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway.
Background Aims:
Osteosarcoma (OS) is a rare cancer affecting children and young adults with a good prognosis when localized. Nevertheless, primary metastases or metastatic relapses are associated with high mortality, underlying the need for novel treatment strategies. Immunotherapy, and more recently Chimeric antigen receptor (CAR)-based therapy, is being investigated as a new approach for the management of solid tumors, although clinical results in OS have so far been limited.
Methods:
We developed a second-generation CAR (OSCAR-3), derived from the TP-3 hybridoma and targeting ALPL-1, an isoform of alkaline phosphatase selectively expressed in OS.
Results:
Stable OSCAR-3 expression in T cells demonstrated potent anti-tumor activity in pre-clinical models. To enable safer clinical translation, we further engineered OSCAR-3 as an mRNA-based CAR. OSCAR-3 mRNA CAR T cells maintained cytotoxic activity in vitro and in vivo, and, importantly, delayed tumor progression in OS patient-derived xenograft models.
Conclusions:
These findings support the further development of OSCAR-3 mRNA CAR T cells as a strategic approach that prioritizes safety over persistence for first-in-human studies, while preserving the ability to reduce tumor growth.
