ArticleProceedings of the National Academy of Sciences of the United States of America2020
A conformation-specific ON-switch for controlling CAR T cells with an orally available drug.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 2 of them syntheses 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
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Mapping the clinical landscape of multifunctional CAR T cells: Targets, trends, and synergies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Pooled it
- Chimeric Antigen Receptor (CAR)-T Cell Immunotherapy Against Thoracic Malignancies: Challenges and Opportunities.Frontiers in immunology · 2022Pooled it
- A Drug-Gated, Modular STAb-T Immunotherapy With External Control.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Genetic Code Expanded T Cell for Controllable Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- In vivo CAR-M therapy: advancing precision delivery and programmable immune remodeling.Cell communication and signaling : CCS · 2026Review
- Combining Small-Molecular Compounds With CAR T-Cell Therapy: Novel Strategies for Enhanced Cancer Immunotherapy.Cancer innovation · 2026Review
- Engineering and Adapting Disulfide-Containing Proteins to Enable Intracellular Functionality.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Advancements and expanding applications of CAR-T cell therapy.Frontiers in immunology · 2026Review
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- De Novo Design of High-Performance Cortisol Luminescent Biosensors.Journal of the American Chemical Society · 2025Article
- Novel strategies to manage CAR-T cell toxicity.Nature reviews. Drug discovery · 2025Review
- Ligand-induced assembly of antibody variable fragments for the chemical regulation of biological processes.Cell chemical biology · 2025Article
- Advancing Immunotherapy in Pancreatic Cancer: A Brief Review of Emerging Adoptive Cell Therapies.Cancers · 2025Review
- Tracing the development of CAR-T cell design: from concept to next-generation platforms.Frontiers in immunology · 2025Review
- Multiplex engineering and multifunction T cells for precise and effective immunotherapies.Frontiers in immunology · 2025Review
- Myeloid cells meet CD8Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Dual ON/OFF-switch chimeric antigen receptor controlled by two clinically approved drugs.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors.Cellular & molecular immunology · 2024Review
- T cell-redirecting therapies in hematological malignancies: Current developments and novel strategies for improved targeting.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
3 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
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Molecular ON-switches in which a chemical compound induces protein-protein interactions can allow cellular function to be controlled with small molecules. ON-switches based on clinically applicable compounds and human proteins would greatly facilitate their therapeutic use. Here, we developed an ON-switch system in which the human retinol binding protein 4 (hRBP4) of the lipocalin family interacts with engineered hRBP4 binders in a small molecule-dependent manner. Two different protein scaffolds were engineered to bind to hRBP4 when loaded with the orally available small molecule A1120. The crystal structure of an assembled ON-switch shows that the engineered binder specifically recognizes the conformational changes induced by A1120 in two loop regions of hRBP4. We demonstrate that this conformation-specific ON-switch is highly dependent on the presence of A1120, as demonstrated by an ∼500-fold increase in affinity upon addition of the small molecule drug. Furthermore, the ON-switch successfully regulated the activity of primary human CAR T cells in vitro. We anticipate that lipocalin-based ON-switches have the potential to be broadly applied for the safe pharmacological control of cellular therapeutics.
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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.