ArticleCancer immunology research2015
CAR-T Cells Inflict Sequential Killing of Multiple Tumor Target Cells.
Article in Cancer immunology research, 2015. 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 100 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
100 citing papers in PubMed, 145 citations in OpenAlex.
- Optimized tandem CD19/CD20 CAR-engineered T cells in refractory/relapsed B-cell lymphoma.Blood · 2020Trial
- Advances and challenges in CAR-T cell therapy for breast cancer: from molecular design to clinical application.Cancer causes & control : CCC · 2026Review
- Resetting autoimmune disease with CAR cell therapies.Nature medicine · 2026Review
- Article
- The Evolving Landscape of CAR T-Cell Therapy in Autoimmune Diseases: A State-of-the-Art Review (2025).Clinical reviews in allergy & immunology · 2026Review
- Clinical progress of engineered cellular immunotherapies for autoimmunity.Nature biotechnology · 2026Review
- Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Nanobody-Engineered CLL-1 CAR T Cells: Optimizing Tumor-Specific Cytotoxicity and Minimizing Off-Tumor Toxicity.Cancer research communications · 2026Article
- TIPE2 knockdown enhances the anti-tumor efficacy of NKG2D CAR-T cells against pancreatic cancer via activating NF-κb signaling pathway.Journal of translational medicine · 2026Article
- Optimally engineered HLA/peptide-specific CAR-T cells outperform TCR-T cells to eradicate solid tumors.Science advances · 2026Article
- CAR-Cell Therapy for Autoimmune Diseases: From the Laboratory to Clinical Practice.Journal of immunology research · 2026Review
- Endoglin-Directed CAR T Cells Comprehensively Target Tumors in Advanced Sarcomas.Cancer immunology research · 2025Article
- Clinical and molecular dissection of CAR T cell resistance in pancreatic cancer.Cell reports. Medicine · 2025Article
- Immunological synapse: structures, molecular mechanisms and therapeutic implications in disease.Signal transduction and targeted therapy · 2025Review
- Mimicking the TCR immune synapse for improved CAR-T cell function.Cell research · 2025Article
- CAR T-cell therapy in hematologic and solid malignancies: mechanisms, clinical applications, and future directions.Medical oncology (Northwood, London, England) · 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
- CAR Binders Affect CAR T-cell Tonic Signaling, Durability, and Sensitivity to Target.Cancer immunology research · 2025Article
- CAR-T cell therapy for juvenile-onset autoimmune diseases: a promising future?Arthritis research & therapy · 2025Review
- Novel B7-H3 CAR T cells show potent antitumor effects in glioblastoma: a preclinical study.Journal for immunotherapy of cancer · 2025Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adoptive therapy with chimeric antigen receptor (CAR) T cells shows great promise clinically. However, there are important aspects of CAR-T-cell biology that have not been explored, particularly with respect to the kinetics of activation, immune synapse formation, and tumor cell killing. Moreover, the effects of signaling via the endogenous T-cell receptor (TCR) or CAR on killing kinetics are unclear. To address these issues, we developed a novel transgenic mouse (designated CAR.OT-I), in which CD8(+) T cells coexpressed the clonogenic OT-I TCR, recognizing the H-2K(b)-presented ovalbumin peptide SIINFEKL, and an scFv specific for human HER2. Primed CAR.OT-I T cells were mixed with SIINFEKL-pulsed or HER2-expressing tumor cells and visualized in real-time using time-lapse microscopy. We found that engagement via CAR or TCR did not affect cell death kinetics, except that the time from degranulation to CAR-T-cell detachment was faster when CAR was engaged. We showed, for the first time, that individual CAR.OT-I cells can kill multiple tumor cells ("serial killing"), irrespective of the mode of recognition. At low effector:target ratios, the tumor cell killing rate was similar via TCR or CAR ligation over the first 20 hours of coincubation. However, from 20 to 50 hours, tumor cell death mediated through CAR became attenuated due to CAR downregulation throughout the time course. Our study provides important insights into CAR-T-tumor cell interactions, with implications for single- or dual receptor-focused T-cell therapy.
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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.