ArticlePloS one2015
Evaluation of Intracellular Signaling Downstream Chimeric Antigen Receptors.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Ligand-based CAR-T cell: Different strategies to drive T cells in future new treatments.Frontiers in immunology · 2022Pooled it
- Single-Cell RNA Analysis Reveals Cell-Intrinsic Functions of CAR T Cells Correlating with Response in a Phase II Study of Lymphoma Patients.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- T-cell protrusions enable fast, localised initiation of chimeric antigen receptor signalling.The EMBO journal · 2026Article
- CD147 regulates CD8iScience · 2026Article
- CD30 as a Target Molecule in the Diagnosis and Therapy of Lymphomas.American journal of hematology · 2026Review
- CAR-T Cell Therapy: Pioneering Immunotherapy Paradigms in Cancer Treatment.Current pharmaceutical biotechnology · 2026Review
- Discordant CAR-T cell signaling: implications of divergence from physiological T cell activation.Journal of translational medicine · 2025Review
- From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy.Journal of translational medicine · 2025Review
- 2B4 co-stimulation and dasatinib modulation enhance anti-CD19 CAR-NK-92 cell cytotoxicity.Frontiers in immunology · 2025Article
- CAR-T cells based on a TCR mimic nanobody targeting HPV16 E6 exhibit antitumor activity against cervical cancer.Molecular therapy. Oncology · 2024Article
- Generation of antitumor chimeric antigen receptors incorporating T cell signaling motifs.Science signaling · 2024Article
- Regulation of temporal cytokine production by co-stimulation receptors in TCR-T cells is lost in CAR-T cells.Immunotherapy advances · 2024Article
- Multiplex interrogation of the NK cell signalome reveals global downregulation of CD16 signaling during lentivirus infection through an IL-18/ADAM17-dependent mechanism.PLoS pathogens · 2023Article
- Complexities in comparing the impact of costimulatory domains on approved CD19 CAR functionality.Journal of translational medicine · 2023Review
- Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.Journal of translational medicine · 2023Review
- Tuning CARs: recent advances in modulating chimeric antigen receptor (CAR) T cell activity for improved safety, efficacy, and flexibility.Journal of translational medicine · 2023Review
- Toward high-throughput engineering techniques for improving CAR intracellular signaling domains.Frontiers in bioengineering and biotechnology · 2023Article
- Analysis of causes for poor persistence of CAR-T cell therapyFrontiers in immunology · 2023Review
- Learning from TCR Signaling and Immunological Synapse Assembly to Build New Chimeric Antigen Receptors (CARs).International journal of molecular sciences · 2022Review
- Co-Stimulatory Receptor Signaling in CAR-T Cells.Biomolecules · 2022Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
CD19-targeting CAR T cells have shown potency in clinical trials targeting B cell leukemia. Although mainly second generation (2G) CARs carrying CD28 or 4-1BB have been investigated in patients, preclinical studies suggest that third generation (3G) CARs with both CD28 and 4-1BB have enhanced capacity. However, little is known about the intracellular signaling pathways downstream of CARs. In the present work, we have analyzed the signaling capacity post antigen stimulation in both 2G and 3G CARs. 3G CAR T cells expanded better than 2G CAR T cells upon repeated stimulation with IL-2 and autologous B cells. An antigen-driven accumulation of CAR+ cells was evident post antigen stimulation. The cytotoxicity of both 2G and 3G CAR T cells was maintained by repeated stimulation. The phosphorylation status of intracellular signaling proteins post antigen stimulation showed that 3G CAR T cells had a higher activation status than 2G. Several proteins involved in signaling downstream the TCR were activated, as were proteins involved in the cell cycle, cell adhesion and exocytosis. In conclusion, 3G CAR T cells had a higher degree of intracellular signaling activity than 2G CARs which may explain the increased proliferative capacity seen in 3G CAR T cells. The study also indicates that there may be other signaling pathways to consider when designing or evaluating new generations of CARs.
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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.