ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Chimeric Antigen Receptor T Cell with an Inducible Caspase-9 Suicide Gene Eradicates Uveal Melanoma Liver Metastases via B7-H3 Targeting.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Gene Therapy Strategies for Uveal Melanoma: Adeno-associated Virus Delivery Challenges and Translational Opportunities.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Cellular immunotherapy in melanoma: the next frontier in cancer treatment.Journal of experimental & clinical cancer research : CR · 2026Review
- B7-H3 CAR T cells eradicate intrahepatic cholangiocarcinoma and induce durable response.Journal of experimental & clinical cancer research : CR · 2026Article
- Combination of YAP inhibition and photodynamic therapy induces dual DNA damage and activates STING pathway to enhance immunotherapy in uveal melanoma.Redox biology · 2026Article
- Bispecific T-Cell Engagers, Cell Therapies, and Other Non-Checkpoint Immunotherapies for Metastatic Uveal Melanoma: A Narrative Review.Journal of clinical medicine · 2026Review
- Clinical Molecular Pathology and Treatment Developments in Advanced Uveal Melanoma: State of the Art.Oncology research · 2026Review
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- Using the iCasp9 suicide strategy to control the growth and function of genome-edited B cells with redirected antigen specificity.Molecular therapy. Oncology · 2025Article
- Mesothelin is a surface antigen present on human meningioma and can be effectively targeted by CAR T-cells.Neuro-oncology · 2025Article
- B7-H3 and CSPG4-targeted CAR T cells as potent effectors in anaplastic thyroid cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- Advances and obstacles of T cell-based immunotherapy in gynecological malignancies.Molecular cancer · 2025Review
- Metastatic hepatic carcinoma: Mechanisms, emerging therapeutics, and future perspectives.iScience · 2025Review
- IFN-γ-mediated suppression of Caspase-7 exacerbates acute lung injury induced by CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Patient-derived organotypic tumor spheroids, tumoroids, and organoids: advancing immunotherapy using state-of-the-art 3D tumor model systems.Lab on a chip · 2025Review
- Review
- TBK1 Targeting Is Identified as a Therapeutic Strategy to Enhance CAR T-Cell Efficacy Using Patient-Derived Organotypic Tumor Spheroids.Cancer immunology research · 2025Article
- Multiplex engineering and multifunction T cells for precise and effective immunotherapies.Frontiers in immunology · 2025Review
- Checkmate awaiting strategy: unlocking the potential of chimeric antigen receptor T-cell therapy in uveal melanoma.Frontiers in oncology · 2025Article
- From spheroids to organoids: next-generation models for CAR-T cell therapy research in solid tumors.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
purposeUveal melanoma (UM) is the most common intraocular malignant tumor. Despite successful treatment of the primary tumor, about 50% of patients will recur with systemic diseases for which there are no effective treatment strategies. Here we investigated the preclinical efficacy of a chimeric antigen receptor (CAR) T-cell-based immunotherapy targeting B7-H3. EXPERIMENTAL
designB7-H3 expression on primary and metastatic human UM samples and cell lines was assessed by RNA sequencing, flow cytometry, and immunohistochemistry. Antitumor activity of CAR T cells targeting B7-H3 was tested in vitro with UM cell lines, patient-derived organotypic tumor spheroids from patients with metastatic UM, and in immunodeficient and humanized murine models.
resultsB7-H3 is expressed at high levels in >95% UM tumor cells in vitro and in vivo. We generated a B7-H3 CAR with an inducible caspase-9 (iCas9) suicide gene controlled by the chemical inducer of dimerization AP1903, which effectively kills UM cells in vitro and eradicates UM liver metastases in murine models. Delivery of iCas9.B7-H3 CAR T cells in experimental models of UM liver metastases demonstrates a durable antitumor response, even upon tumor rechallenge or in the presence of a significant metastatic disease burden. We demonstrate effective iCas9.B7-H3 CAR T-cell elimination in vitro and in vivo in response to AP1903. Our studies demonstrate more effective tumor suppression with iCas9.B7-H3 CAR T cells as compared to a B7-H3-targeted humanized monoclonal antibody.
conclusionsThese studies support a phase I clinical trial with iCas9.B7-H3 CAR T cells to treat patients with metastatic UM.
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