ArticleCancer research2011
In vivo persistence, tumor localization, and antitumor activity of CAR-engineered T cells is enhanced by costimulatory signaling through CD137 (4-1BB).
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 164 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
164 citing papers in PubMed, 1 synthesis or guideline pooled it, 294 citations in OpenAlex.
- The efficacy and safety of anti-CD19/CD20 chimeric antigen receptor- T cells immunotherapy in relapsed or refractory B-cell malignancies:a meta-analysis.BMC cancer · 2018Pooled it
- Investigating the role of costimulatory domains in enhancing CAR-T cell persistence in TNBC.Cancer gene therapy · 2026Review
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Dual Targeting of FAP-Directed Nanoparticles and FRα-Specific CAR-T Cells Induces Additive Anti-Tumor Effects in Triple-Negative Breast Cancer.International journal of biological sciences · 2026Article
- Targeting Folate Receptors for the Detection and Selective Treatment of Cancer: Advanced Precision Oncology in Practice.International journal of biological sciences · 2026Review
- Review
- Syngeneic CAR T cells engineered for persistent delivery of desired proteins.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.Molecular therapy. Nucleic acids · 2025Review
- Article
- Folate Receptor Alpha-A Secret Weapon in Ovarian Cancer Treatment?International journal of molecular sciences · 2024Review
- Chimeric antigen receptor-T cells targeting epithelial cell adhesion molecule antigens are effective in the treatment of colorectal cancer.BMC gastroenterology · 2024Article
- Bispecific CAR-T cells targeting FAP and GPC3 have the potential to treat hepatocellular carcinoma.Molecular therapy. Oncology · 2024Article
- Control of the antitumour activity and specificity of CAR T cells via organic adapters covalently tethering the CAR to tumour cells.Nature biomedical engineering · 2024Article
- Identification and characterisation of novel CAR-T cells to target IL13Rα2 positive human glioma in vitro and in vivo.Clinical and translational medicine · 2024Article
- CD137+ tumor infiltrating lymphocytes predicts ovarian cancer survival.Gynecologic oncology · 2024Article
- A novel lentiviral vector-based approach to generate chimeric antigen receptor T cells targetingmBio · 2024Article
- Chimeric antigen receptor-based natural killer cell immunotherapy in cancer: from bench to bedside.Cell death & disease · 2024Review
- Advances in the treatment of malignant ascites in China.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Review
- CAR-T cell therapy: developments, challenges and expanded applications from cancer to autoimmunity.Frontiers in immunology · 2024Review
- F77 antigen is a promising target for adoptive T cell therapy of prostate cancer.Biochemical and biophysical research communications · 2023Article
104 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Human T cells engineered to express a chimeric antigen receptor (CAR) specific for folate receptor-α (FRα) have shown robust antitumor activity against epithelial cancers in vitro but not in the clinic because of their inability to persist and home to tumor in vivo. In this study, CARs were constructed containing a FRα-specific scFv (MOv19) coupled to the T-cell receptor CD3ζ chain signaling module alone (MOv19-ζ) or in combination with the CD137 (4-1BB) costimulatory motif in tandem (MOv19-BBζ). Primary human T cells transduced to express conventional MOv19-ζ or costimulated MOv19-BBζ CARs secreted various proinflammatory cytokines, and exerted cytotoxic function when cocultured with FRα(+) tumor cells in vitro. However, only transfer of human T cells expressing the costimulated MOv19-BBζ CAR mediated tumor regression in immunodeficient mice bearing large, established FRα(+) human cancer. MOv19-BBζ CAR T-cell infusion mediated tumor regression in models of metastatic intraperitoneal, subcutaneous, and lung-involved human ovarian cancer. Importantly, tumor response was associated with the selective survival and tumor localization of human T cells in vivo and was only observed in mice receiving costimulated MOv19-BBζ CAR T cells. T-cell persistence and antitumor activity were primarily antigen-driven; however, antigen-independent CD137 signaling by CAR improved T-cell persistence but not antitumor activity in vivo. Our results show that anti-FRα CAR outfitted with CD137 costimulatory signaling in tandem overcome issues of T-cell persistence and tumor localization that limit the conventional FRα T-cell targeting strategy to provide potent antitumor activity in vivo.
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What OpenQuestion holds
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.