ArticleCancer immunology research2015
Generation of Potent T-cell Immunotherapy for Cancer Using DAP12-Based, Multichain, Chimeric Immunoreceptors.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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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.
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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
76 citing papers in PubMed, 113 citations in OpenAlex.
- Preclinical evaluation of homodimeric FAPI target modules for UniCAR-mediated targeting of FAP-expressing tumor and stromal cells.Oncoimmunology · 2026Article
- The Evolution of FAP-Targeted CAR T-Cell Therapy in Solid Tumors: From Immunotherapy to Immunotheranostic Applications.International journal of molecular sciences · 2026Review
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- HER2-specific synthetic antigen receptor T cell therapy synergizes with radiotherapy to provide improved antitumor efficacy in non-small cell lung cancer.Journal of leukocyte biology · 2026Article
- Engineering a juxtamembrane-targeting CAR T-cell against mesothelin: a novel binder resilient to shed antigen for enhanced efficacy against ovarian and pancreatic cancer.Frontiers in immunology · 2026Article
- A novel CD3ε fusion receptor allows T cell engager use in TCR-less allogeneic CAR T cells to improve activity and prevent antigen escape.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Engineering resilient CAR T cells for immunosuppressive environment.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Concept CARs are picking up speed.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- MARC, a novel modular chimeric antigen receptor, improves T cell-based cancer immunotherapies by preventing early T cell exhaustion and enhancing persistence.Journal for immunotherapy of cancer · 2025Article
- Article
- Expanding the CAR toolbox with high throughput screening strategies for CAR domain exploration: a comprehensive review.Journal for immunotherapy of cancer · 2025Review
- Effectors of the Future: Universal Chimeric Antigen Receptor.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- The development and application of chimeric antigen receptor natural killer (CAR-NK) cells for cancer therapy: current state, challenges and emerging therapeutic advances.Experimental hematology & oncology · 2024Review
- Solid tumor immunotherapy using NKG2D-based adaptor CAR T cells.Cell reports. Medicine · 2024Article
- Efficacy and safety of novel multiple-chain DAP-CAR-T cells targeting mesothelin in ovarian cancer and mesothelioma: a single-arm, open-label and first-in-human study.Genome medicine · 2024Article
- Electrophilic proximity-inducing synthetic adapters enhance universal T cell function by covalently enforcing immune receptor signaling.Molecular therapy. Oncology · 2024Article
- The physical landscape of CAR-T synapse.Biophysical journal · 2024Review
- The Glucose Transporter 5 Enhances CAR-T Cell Metabolic Function and Anti-tumour Durability.Research square · 2024Article
- CAR-T Cell Therapy in Ovarian Cancer: Where Are We Now?Diagnostics (Basel, Switzerland) · 2024Review
- Effects of methionine deficiency on B7H3-DAP12-CAR-T cells in the treatment of lung squamous cell carcinoma.Cell death & disease · 2024Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Chimeric antigen receptors (CAR) bearing an antigen-binding domain linked in cis to the cytoplasmic domains of CD3ζ and costimulatory receptors have provided a potent method for engineering T-cell cytotoxicity toward B-cell leukemia and lymphoma. However, resistance to immunotherapy due to loss of T-cell effector function remains a significant barrier, especially in solid malignancies. We describe an alternative chimeric immunoreceptor design in which we have fused a single-chain variable fragment for antigen recognition to the transmembrane and cytoplasmic domains of KIR2DS2, a stimulatory killer immunoglobulin-like receptor (KIR). We show that this simple, KIR-based CAR (KIR-CAR) triggers robust antigen-specific proliferation and effector function in vitro when introduced into human T cells with DAP12, an immunotyrosine-based activation motifs-containing adaptor. T cells modified to express a KIR-CAR and DAP12 exhibit superior antitumor activity compared with standard first- and second-generation CD3ζ-based CARs in a xenograft model of mesothelioma highly resistant to immunotherapy. The enhanced antitumor activity is associated with improved retention of chimeric immunoreceptor expression and improved effector function of isolated tumor-infiltrating lymphocytes. These results support the exploration of KIR-CARs for adoptive T-cell immunotherapy, particularly in immunotherapy-resistant solid tumors.
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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.