ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
A genetically encoded protein tag for control and quantitative imaging of CAR T cell therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Reversible control of CAR T cells through PROTAC compound targeting bromodomain mutant.Molecular therapy. Oncology · 2026Article
- Tunable gene control via RNA splicing with a clinically approved small molecule.Nature communications · 2026Article
- A programmable genetic platform for engineering noninvasive biosensors.Science advances · 2026Article
- Photocontrolled trimethoprim PROTACs targeting the eDHFR protein tag.Nature communications · 2025Article
- Small-molecule control of CAR T cells.Nature reviews. Chemistry · 2025Review
- Practical considerations for clinical translation of PET imaging of adoptive cell therapies.Npj imaging · 2025Review
- A programmable genetic platform for engineering noninvasive biosensors.bioRxiv : the preprint server for biology · 2025Article
- Recent developments in translational imaging of in vivo gene therapy outcomes.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Monitoring mRNA vaccine antigen expression in vivo using PET/CT.Nature communications · 2025Article
- Low-dose targeted radionuclide therapy synergizes with CAR T cells and enhances tumor response.Frontiers in immunology · 2024Article
- Precision oncology revolution: CRISPR-Cas9 and PROTAC technologies unleashed.Frontiers in genetics · 2024Review
- Tagging CAR-T cells to enable control and quantitative imaging.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapy has been successful for hematological malignancies. Still, a lack of efficacy and potential toxicities have slowed its application for other indications. Furthermore, CAR T cells undergo dynamic expansion and contraction in vivo that cannot be easily predicted or controlled. Therefore, the safety and utility of such therapies could be enhanced by engineered mechanisms that engender reversible control and quantitative monitoring. Here, we use a genetic tag based on the enzyme Escherichia coli dihydrofolate reductase (eDHFR), and derivatives of trimethoprim (TMP) to modulate and monitor CAR expression and T cell activity. We fused eDHFR to the CAR C terminus, allowing regulation with TMP-based proteolysis-targeting chimeric small molecules (PROTACs). Fusion of eDHFR to the CAR does not interfere with cell signaling or its cytotoxic function, and the addition of TMP-based PROTACs results in a reversible and dose-dependent inhibition of CAR activity via the proteosome. We show the regulation of CAR expression in vivo and demonstrate imaging of the cells with TMP radiotracers. In vitro immunogenicity assays using primary human immune cells and overlapping peptide fragments of eDHFR showed no memory immune repertoire for eDHFR. Overall, this translationally-orientied approach allows for temporal monitoring and image-guided control of cell-based therapies.
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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.