ArticleSignal transduction and targeted therapy2025
Chimeric antigen receptor with novel intracellular modules improves antitumor performance of T cells.
Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Next-generation CAR-T cell therapy against cancer: precision engineering, programmable immunity, and emerging clinical frontiers.Journal of the Egyptian National Cancer Institute · 2026Review
- B cells in cancer: functions, mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- Microfluidic-based rapid generation of chimeric antigen receptor T cells improves low-multiplicity-of-infection transduction efficiency while preserving functional activity.Journal of translational medicine · 2026Article
- Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.Signal transduction and targeted therapy · 2026Review
- Humanized and Charge-Optimized CSPG4-Specific CAR-T Cells show Enhanced Efficacy against Head and Neck Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- CRISPR/Cas9 Genome Editing in Oncology: Mechanisms, Therapeutic Platforms and Translational Challenges.Molecular biotechnology · 2026Review
- Bispecific CD37-Siglec6 CAR‑T cells exhibit enhanced anti‑leukemic activity and reduced exhaustion in acute myeloid leukemia xenograft models.Journal of translational medicine · 2026Article
- Optimization of THP-1-CAR monocytes utilizing CD32a signaling phagocytosis for antigen-specific T cell activation.Scientific reports · 2026Article
- Systematic optimization of PD-L1 and CLDN18.2 CAR-T designs identifies a bicistronic dual-target, double-CD3ζ architecture with enhanced antitumor activity in gastric cancer.Frontiers in immunology · 2026Article
- Limitations of CAR-T-Cell Therapy in Hematologic Malignancies: Focusing on Antigen Escape and T-Cell Dysfunction.International journal of molecular sciences · 2025Review
- Selinexor Reduces the Immunosuppression of Macrophages and Synergizes With CD19 CAR-T Cells Against B-Cell Lymphoma.Cancer science · 2025Article
- Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.Cellular & molecular immunology · 2025Review
- Targets for CAR Therapy in Multiple Myeloma.International journal of molecular sciences · 2025Review
- Tailoring CAR surface density and dynamics to improve CAR-T cell therapy.Journal for immunotherapy of cancer · 2025Review
- Optimization of CAR-T therapy based on metabolic remodeling of the tumor immune microenvironment in diffuse large B-cell lymphoma.American journal of cancer research · 2025Review
- Fine-tuning signal strength in CD5 CAR-NK cells for targeted T cell cancer therapy.Frontiers in immunology · 2025Article
- Activation of FCGR2A enhances the antitumor efficacy of hPSC-derived CAR-M.Frontiers in cell and developmental biology · 2025Article
- The epidemiology, etiology, and future prophylactic options for cancers in Mainland China.Frontiers in oncology · 2025Review
- The TCR and LCK: foundations for T-cell activation and therapeutic innovation.Frontiers in immunology · 2025Review
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Authors and funding
14 authors.
Funding
Abstract
The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T (CAR-T) cell therapy in diverse tumors. Conventional CARs employ an intracellular domain (ICD) from the ζ subunit of CD3 as a signaling module, and it is largely unknown how alternative CD3 chains potentially contribute to CAR design. Here, we obtained a series of CAR-T cells against HER2 and mesothelin using a domain comprising a single immunoreceptor tyrosine-based activation motif from different CD3 subunits as the ICD of CARs. While these reconstituted CARs conferred sufficient antigen-specific cytolytic activity on equipped T cells, they elicited low tonic signal, ameliorated the exhaustion and promoted memory differentiation of these cells. Intriguingly, the CD3ε-derived ICD outperformed others in generation of CAR-T cells that produced minimized cytokines. Mechanistically, CD3ε-based CARs displayed a restrained cytomembrane expression on engineered T cells, which was ascribed to endoplasmic reticulum retention mediated by the carboxyl terminal basic residues. The present study demonstrated the applicability of CAR reconstitution using signaling modules from different CD3 subunits, and depicted a novel pattern of CAR expression that reduces cytokine release, thus paving a way for preparation of CAR-T cells displaying improved safety and persistence against diverse tumor antigens.
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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.