ArticleCellular & molecular immunology2024
SMAD7 expression in CAR-T cells improves persistence and safety for solid tumors.
Article in Cellular & molecular immunology, 2024. 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 31 papers.
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Who cites it
31 citing papers in PubMed, 32 citations in OpenAlex.
- Overcoming T cell exhaustion and senescence in CAR T cell therapy for solid tumors.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Enhancing HIV-1-specific CAR-T cell functional activity by treatment with a novel cytokine-based scaffold with IL-15 superagonist and TGF-β-neutralizing activity.Journal of virology · 2026Article
- Recent advances in molecular mechanisms to improve the efficacy of CAR-T cell therapy for viral diseases, cancer, and autoimmune diseases.Stem cell research & therapy · 2026Review
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.Journal of translational medicine · 2026Review
- Harnessing Tumor Organoids to Revolutionize Immunotherapy Research.Cancer medicine · 2026Review
- Asiaticoside enhances the antitumor efficacy of MSLN-targeted CAR-T cells in ovarian cancer.Journal of translational medicine · 2026Article
- IL-7/IL-15/IL-21 cytokine-fusion scaffold generates highly functional CAR T cells enriched in long-lived T memory stem cells.Science advances · 2026Article
- Obstacles and improvement strategies for CAR-T cell therapy in solid tumors.Discover oncology · 2026Review
- Article
- The Roles of ProteinCancer communications (London, England) · 2026Review
- Organoid models: reshaping the paradigm for precision development and evaluation of CAR-T cell therapies.Frontiers in bioengineering and biotechnology · 2026Review
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Aging-associated transcriptional programs in T cells signify constituents of TGF-β signaling for immunosenescence.BMC biology · 2025Article
- Limitations of CAR-T-Cell Therapy in Hematologic Malignancies: Focusing on Antigen Escape and T-Cell Dysfunction.International journal of molecular sciences · 2025Review
- INO80/SWR remodelers regulate Pol II transcription through BRD2 and chromatin landscape.Nucleic acids research · 2025Article
- SMAD7: riding on fibrosis-limiting routes and beyond.EMBO molecular medicine · 2025Review
- Organoid models in oncology: advancing precision cancer therapy and vaccine development.Cancer biology & medicine · 2025Review
- Chimeric antigen receptor with novel intracellular modules improves antitumor performance of T cells.Signal transduction and targeted therapy · 2025Article
- Precision Reprogramming in CAR-T Cell Therapy: Innovations, Challenges, and Future Directions of Advanced Gene Editing.International journal of biological sciences · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the tremendous progress of chimeric antigen receptor T (CAR-T) cell therapy in hematological malignancies, their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenvironment (TME) and systemic toxicity caused by excessive cytokine release. As a key regulator of the immunosuppressive TME, TGF-β promotes cytokine synthesis via the NF-κB pathway. Here, we coexpressed SMAD7, a suppressor of TGF-β signaling, with a HER2-targeted CAR in engineered T cells. These novel CAR-T cells displayed high cytolytic efficacy and were resistant to TGF-β-triggered exhaustion, which enabled sustained tumoricidal capacity after continuous antigen exposure. Moreover, SMAD7 substantially reduced the production of inflammatory cytokines by antigen-primed CAR-T cells. Mechanistically, SMAD7 downregulated TGF-β receptor I and abrogated the interplay between the TGF-β and NF-κB pathways in CAR-T cells. As a result, these CAR-T cells persistently inhibited tumor growth and promoted the survival of tumor-challenged mice regardless of the hostile tumor microenvironment caused by a high concentration of TGF-β. SMAD7 coexpression also enhanced CAR-T-cell infiltration and persistent activation in patient-derived tumor organoids. Therefore, our study demonstrated the feasibility of SMAD7 coexpression as a novel approach to improve the efficacy and safety of CAR-T-cell therapy for solid tumors.
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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.