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Updated: Feb 1, 2026

LINE-1 Methylation Analysis in Mesenchymal Stem Cells Treated with Osteosarcoma-Derived Extracellular Vesicles
Published on: February 1, 2020
Treating osteosarcoma with CAR T cells
Hakan Köksal1, Elisabeth Müller1, Else Marit Inderberg1
1Laboratory of Translational Research & Immunomonitoring, Section for Cellular Therapy, Department of Oncology, Oslo University Hospital, Oslo, Norway.
Abstract:
Novel therapies to treat patients with solid cancers that have developed resistance to chemotherapy represent unmet needs of considerable dimensions. In the present review, we will address the attempts to develop chimeric antigen receptor (CAR) targeted immunotherapy against osteosarcoma (OS). This aggressive cancer displays its peak incidence in children and young adults. The main cause of patient death is lung metastases with a 5-year survival as low as 5%-10% in the primary metastatic setting and 30% in the relapse situation, respectively. Effective adjuvant combination chemotherapy introduced more than 40 years ago improved the survival rates from below 20% to around 60% in patients; however, since then, no major breakthroughs have been made. The use of immune checkpoint inhibitors has been disappointing in OS, while other types of immunotherapies such as CAR T cells remain largely unexplored. Indeed, for CAR T-cell therapy to be efficacious, two main criteria need to be fulfilled: (a) CAR T cells should target an epitope selectively expressed on the cell surface of OS in order to prevent toxicities in normal tissues and (b) the target should also be widely expressed on OS metastases. These challenges have already been undertaken in OS and illustrate the difficulties in developing tomorrow's CAR-T treatment in a solid tumour. We will discuss the experiences with CAR-T therapy development and efficacy to combat the clinical challenges in OS.
Insights
Chimeric antigen receptor (CAR) T-cell therapy shows promise for treating osteosarcoma, a challenging pediatric cancer. Overcoming challenges in targeting cancer cells while sparing healthy tissues is key to developing effective CAR T-cell treatments for solid tumors.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Research
Background:
- Osteosarcoma (OS) is an aggressive pediatric cancer with poor survival rates, especially with lung metastases.
- Current chemotherapy has not seen major breakthroughs in over 40 years, and immune checkpoint inhibitors have been disappointing in OS.
- Chimeric antigen receptor (CAR) T-cell therapy remains largely unexplored in OS, presenting an unmet need for novel treatments.
Purpose of the Study:
- To review attempts at developing CAR T-cell immunotherapy against osteosarcoma.
- To discuss the challenges and experiences in developing CAR T-cell therapy for solid tumors like OS.
- To explore the potential efficacy of CAR T-cell therapy in combating clinical challenges in OS.
Main Methods:
- Review of existing literature on CAR T-cell therapy development for osteosarcoma.
- Analysis of challenges in targeting cancer-specific epitopes on solid tumors.
- Discussion of criteria for efficacious CAR T-cell therapy in OS, including target selectivity and metastasis coverage.
Main Results:
- Developing CAR T-cell therapy for OS faces significant hurdles, particularly in identifying targets selectively expressed on OS cells and their metastases.
- The review highlights the difficulties in translating CAR T-cell potential into effective treatments for solid tumors.
- Experiences with CAR T-cell therapy development in OS illustrate the complexities of this approach.
Conclusions:
- CAR T-cell therapy holds potential for osteosarcoma treatment but requires overcoming specific challenges related to target identification and tumor heterogeneity.
- Further research and development are needed to optimize CAR T-cell strategies for solid tumors like OS.
- Addressing the unmet need for novel therapies in osteosarcoma necessitates continued innovation in immunotherapy.
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