ArticleACS synthetic biology2022
Sense-and-Respond Payload Delivery Using a Novel Antigen-Inducible Promoter Improves Suboptimal CAR-T Activation.
Article in ACS synthetic biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Progress in the development of cytokine armoured CAR T cells.Nature reviews. Immunology · 2026Review
- The genome takes the wheel: CAR T with built-in circuits.Immuno-oncology technology · 2026Article
- Auto-inducible expression of chimeric antigen receptor T cells using the NR4A1 promoter.Immunology and cell biology · 2026Article
- Cytokine Engineering in CAR-T Cell Therapy: Next-Generation Strategies.Immune network · 2025Review
- Syngeneic CAR T cells engineered for persistent delivery of desired proteins.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- IL-2-independent expansion, persistence, and antitumor activity in TIL expressing regulatable membrane-bound IL-15.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- SPECIFIC: A systematic framework for engineering cell state-responsive synthetic promoters reveals key regulators of T cell exhaustion.Quantitative biology (Beijing, China) · 2025Article
- Effectors of the Future: Universal Chimeric Antigen Receptor.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- Article
- Stem Loop Mediated Transgene Modulation in Human T Cells.ACS synthetic biology · 2024Article
- Logic-gated and contextual control of immunotherapy for solid tumors: contrasting multi-specific T cell engagers and CAR-T cell therapies.Frontiers in immunology · 2024Review
- CTLA-4 tail fusion enhances CAR-T antitumor immunity.Nature immunology · 2023Article
- Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy.Frontiers in immunology · 2023Review
- Recent progress of gene circuit designs in immune cell therapies.Cell systems · 2022Review
- Secretory co-factors in next-generation cellular therapies for cancer.Frontiers in immunology · 2022Review
- Synthetic biology: at the crossroads of genetic engineering and human therapeutics-a Keystone Symposia report.Annals of the New York Academy of Sciences · 2021Review
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Chimeric antigen receptor (CAR)-T cell therapies demonstrate the clinical potential of lymphocytes engineered with synthetic properties. However, CAR-T cells are ineffective in most solid tumors, partly due to inadequate activation of the infused lymphocytes at the site of malignancy. To selectively enhance antitumor efficacy without exacerbating off-target toxicities, CAR-T cells can be engineered to preferentially deliver immunostimulatory payloads in tumors. Here, we report a novel antigen-inducible promoter for conditional payload expression in primary human T cells. In therapeutic T cell models, the novel NR4A-based promoter induced higher reporter gene expression than the conventional NFAT-based promoter under weakly immunogenic conditions, where payload expression is most needed. Minimal activity was detected from the inducible promoters in the absence of antigen and after withdrawal of stimulation. As a functional proof-of-concept, we used the NR4A-based promoter to express cytokines in an antimesothelin CAR-T model with suboptimal stimulation and observed improved proliferation compared to T cells engineered with the conventional NFAT promoter or CAR alone. Our system achieves CAR-directed payload expression under weakly immunogenic conditions and could enable the next generation of cell therapies with enhanced antitumor efficacy.
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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.