ArticleInternational journal of molecular sciences2021
Structure of the Signal Transduction Domain in Second-Generation CAR Regulates the Input Efficiency of CAR Signals.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- A Systematic Review on PD-1 Blockade and PD-1 Gene-Editing of CAR-T Cells for Glioma Therapy: From Deciphering to Personalized Medicine.Frontiers in immunology · 2021Pooled it
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- CAR T cell therapy for fighting IPF: perspectives on a living drug.Frontiers in immunology · 2026Review
- Advances in Adoptive Cell Therapies in Cancer: From Mechanistic Breakthroughs to Clinical Frontiers and Overcoming Barriers.Medical sciences (Basel, Switzerland) · 2025Review
- Targets for CAR Therapy in Multiple Myeloma.International journal of molecular sciences · 2025Review
- Direct visualization of chimeric antigen receptors on primary human T cells usingFrontiers in immunology · 2025Article
- Current Advances and Challenges in CAR-T Therapy for Hematological and Solid Tumors.ImmunoTargets and therapy · 2025Review
- Harnessing the Transcriptional Signatures of CAR-T-Cells and Leukemia/Lymphoma Using Single-Cell Sequencing Technologies.International journal of molecular sciences · 2024Review
- Article
- Extracellular domain, hinge, and transmembrane determinants affecting surface CD4 expression of a novel anti-HIV chimeric antigen receptor (CAR) construct.bioRxiv : the preprint server for biology · 2023Article
- Emerging Immunotherapy Approaches for Treating Prostate Cancer.International journal of molecular sciences · 2023Review
- Modulation of Radiation Doses and Chimeric Antigen Receptor T Cells: A Promising New Weapon in Solid Tumors-A Narrative Review.Journal of personalized medicine · 2023Review
- Combination of CAR‑T cell therapy and radiotherapy: Opportunities and challenges in solid tumors (Review).Oncology letters · 2023Review
- Scoring model based on the signature of non-m6A-related neoantigen-coding lncRNAs assists in immune microenvironment analysis and TCR-neoantigen pair selection in gliomas.Journal of translational medicine · 2022Article
- Emerging Trends in Immunotherapy for Cancer.Diseases (Basel, Switzerland) · 2022Review
- The Effects of Chimeric Antigen Receptor (CAR) Hinge Domain Post-Translational Modifications on CAR-T Cell Activity.International journal of molecular sciences · 2022Article
- The Impact of the Intracellular Domains of Chimeric Antigenic Receptors on the Properties of CAR T-cells.Acta naturaeArticle
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
T cells that are genetically engineered to express chimeric antigen receptor (CAR) have a strong potential to eliminate tumor cells, yet the CAR-T cells may also induce severe side effects due to an excessive immune response. Although optimization of the CAR structure is expected to improve the efficacy and toxicity of CAR-T cells, the relationship between CAR structure and CAR-T cell functions remains unclear. Here, we constructed second-generation CARs incorporating a signal transduction domain (STD) derived from CD3ζ and a 2nd STD derived from CD28, CD278, CD27, CD134, or CD137, and investigated the impact of the STD structure and signaling on CAR-T cell functions. Cytokine secretion of CAR-T cells was enhanced by 2nd STD signaling. T cells expressing CAR with CD278-STD or CD137-STD proliferated in an antigen-independent manner by their STD tonic signaling. CAR-T cells incorporating CD28-STD or CD278-STD between TMD and CD3ζ-STD showed higher cytotoxicity than first-generation CAR or second-generation CARs with other 2nd STDs. The potent cytotoxicity of these CAR-T cells was not affected by inhibiting the 2nd STD signals, but was eliminated by placing the STDs after the CD3ζ-STD. Our data highlighted that CAR activity was affected by STD structure as well as by 2nd STD signaling.
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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.