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Updated: Jul 27, 2025
A Real-time Potency Assay for Chimeric Antigen Receptor T Cells Targeting Solid and Hematological Cancer Cells
Published on: November 12, 2019
ALPL-1 is a target for chimeric antigen receptor therapy in osteosarcoma
Nadia Mensali1, Hakan Köksal1, Sandy Joaquina1
1Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
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.
Insights
Chimeric antigen receptor (CAR) T-cells targeting ALPL-1 show promise for osteosarcoma (OS) treatment. These CAR T-cells effectively target and kill OS cells in preclinical models, offering a potential new therapy for this challenging cancer.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Osteosarcoma (OS) is an aggressive bone cancer with poor outcomes, especially in recurrent or metastatic cases.
- Current immunotherapies for OS show limited efficacy due to tumor heterogeneity and target protein expression variability.
Purpose of the Study:
- To investigate the potential of chimeric antigen receptor (CAR) T-cells targeting a specific isoform of alkaline phosphatase, ALPL-1, for osteosarcoma treatment.
- To evaluate the efficacy and safety of ALPL-1-targeted CAR T-cells in preclinical osteosarcoma models.
Main Methods:
- Development of a second-generation CAR construct utilizing antibodies specific to OS.
- Transduction of T-cells with the CAR construct targeting ALPL-1.
- In vitro cytotoxicity assays against ALPL-positive OS cells.
- In vivo studies using orthotopic models of primary and metastatic OS.
Main Results:
- CAR T-cells efficiently and specifically targeted ALPL-1, which is highly expressed in primary and metastatic OS.
- Demonstrated effective cytotoxicity against ALPL-positive OS cells in vitro.
- Showed significant efficacy in preclinical orthotopic OS models without observed off-target toxicities.
Conclusions:
- ALPL-1-targeted CAR T-cells represent a promising and specific therapeutic strategy for osteosarcoma.
- These findings support the clinical translation of ALPL-1-targeted CAR T-cell therapy for osteosarcoma patients.
