ArticleFrontiers in immunology2021
A Novel Orthotopic Implantation Technique for Osteosarcoma Produces Spontaneous Metastases and Illustrates Dose-Dependent Efficacy of B7-H3-CAR T Cells.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 30 citations in OpenAlex.
- Targeting Regnase-1 in B7-H3-CAR T cells reprograms the tumor microenvironment and enhances antitumor efficacy for osteosarcoma.Cell reports. Medicine · 2026Article
- Paediatric therapeutic development workshop on osteosarcoma.British journal of cancer · 2026Review
- CAR-T cell therapy for pediatric solid tumors: armored CAR-T cells and beyond.Cancer metastasis reviews · 2026Review
- <p>Tumor microenvironment in bone sarcomas: Implications for immunotherapy and emerging therapeutic vulnerabilities (Review)</p>.Oncology reports · 2026Review
- Exploiting B7-H3: Molecular Insights and Immunotherapeutic Strategies for Osteosarcoma.Bioengineering (Basel, Switzerland) · 2025Review
- Pitfalls and strategies of CAR-T therapy in solid tumors and implications for chordoma treatment.Immunotherapy · 2025Review
- Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.Nature medicine · 2025Article
- Biomimetic Targeted Co-Delivery System Engineered from Genomic Insights for Precision Treatment of Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Osteosarcoma: A comprehensive review of model systems and experimental therapies.Medical research archives · 2024Article
- The efficacy and applicability of chimeric antigen receptor (CAR) T cell-based regimens for primary bone tumors: A comprehensive review of current evidence.Journal of bone oncology · 2024Review
- Redirecting B7-H3.CAR T Cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- CAR T cells redirected to B7-H3 for pediatric solid tumors: Current status and future perspectives.EJC paediatric oncology · 2024Article
- WNT5B drives osteosarcoma stemness, chemoresistance and metastasis.Clinical and translational medicine · 2024Article
- Chimeric antigen receptor T cells in the treatment of osteosarcoma (Review).International journal of oncology · 2024Review
- Immunotherapy of osteosarcoma based on immune microenvironment modulation.Frontiers in immunology · 2024Review
- Targeting B7-H3-A Novel Strategy for the Design of Anticancer Agents for Extracranial Pediatric Solid Tumors Treatment.Molecules (Basel, Switzerland) · 2023Review
- Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment.Bone research · 2023Review
- Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety.Cancer discovery · 2023Article
- Strategies to Overcome Resistance to Immune-Based Therapies in Osteosarcoma.International journal of molecular sciences · 2023Review
- Current status and future challenges of CAR-T cell therapy for osteosarcoma.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The outcome for metastatic pediatric osteosarcoma (OS) remains poor. Thus, there is an urgent need to develop novel therapies, and immunotherapy with CAR T cells has the potential to meet this challenge. However, there is a lack of preclinical models that mimic salient features of human disease including reliable development of metastatic disease post orthotopic OS cell injection. To overcome this roadblock, and also enable real-time imaging of metastatic disease, we took advantage of LM7 OS cells expressing firefly luciferase (LM7.ffLuc). LM7.ffLuc were implanted in a collagen mesh into the tibia of mice, and mice reliably developed orthotopic tumors and lung metastases as judged by bioluminescence imaging and histopathological analysis. Intratibial implantation also enabled surgical removal by lower leg amputation and monitoring for metastases development post-surgery. We then used this model to evaluate the antitumor activity of CAR T cells targeting B7-H3, an antigen that is expressed in a broad range of solid tumors including OS. B7-H3-CAR T cells had potent antitumor activity in a dose-dependent manner and inhibited the development of pulmonary metastases resulting in a significant survival advantage. In contrast T cells expressing an inactive B7-H3-CAR had no antitumor activity. Using unmodified LM7 cells also enabled us to demonstrate that B7-H3-CAR T cells traffic to orthotopic tumor sites. Hence, we have developed an orthotopic, spontaneously metastasizing OS model. This model may improve our ability not only to predict the safety and efficacy of current and next generation CAR T cell therapies but also other treatment modalities for metastatic OS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.