ArticleGene therapy2013
Efficient selection of genetically modified human T cells using methotrexate-resistant human dihydrofolate reductase.
Article in Gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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
24 citing papers in PubMed, 34 citations in OpenAlex.
- Efficient, fratricide free non-viral engineering of CD70-targeted CAR NK cells for hematologic and solid tumor immunotherapy.Molecular therapy. Advances · 2026Article
- Efficient and Traceless Aptamer-Based Serial Selection of Naïve and Early Memory CD8 T Cells for CAR T Cell Therapy.Advanced healthcare materials · 2026Article
- CRISPR/methotrexate-integrated strategy for TCR-T cell engineering with reduced chromosome 14 loss.Molecular therapy. Methods & clinical development · 2025Article
- Intracerebroventricular B7-H3-targeting CAR T cells for diffuse intrinsic pontine glioma: a phase 1 trial.Nature medicine · 2025Article
- Spatial Control of CAR T Cell Activation Using Tumor-Homing Polymers.Journal of the American Chemical Society · 2025Article
- Immunosuppressant therapy averts rejection of allogeneic FKBP1A-disrupted CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Evolution of the clinical-stage hyperactive TcBuster transposase as a platform for robust non-viral production of adoptive cellular therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Homology-independent targeted insertion (HITI) enables guided CAR knock-in and efficient clinical scale CAR-T cell manufacturing.Molecular cancer · 2023Article
- Non-viral chimeric antigen receptor (CAR) T cells going viral.Immuno-oncology technology · 2023Review
- Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety.Cancer discovery · 2023Article
- Genetic engineering of T cells for immunotherapy.Nature reviews. Genetics · 2021Review
- Efficient Enrichment of Gene-Modified Primary T Cells via CCR5-Targeted Integration of Mutant Dihydrofolate Reductase.Molecular therapy. Methods & clinical development · 2018Article
- Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications.Frontiers in immunology · 2017Review
- Antithymidylate resistance enables transgene selection and cell survival for T cells in the presence of 5-fluorouracil and antifolates.Gene therapy · 2016Article
- Article
- Paclitaxel and the dietary flavonoid fisetin: a synergistic combination that induces mitotic catastrophe and autophagic cell death in A549 non-small cell lung cancer cells.Cancer cell international · 2016Article
- Towards in vivo amplification: Overcoming hurdles in the use of hematopoietic stem cells in transplantation and gene therapy.World journal of stem cells · 2015Review
- Dihydrofolate Reductase and Thymidylate Synthase Transgenes Resistant to Methotrexate Interact to Permit Novel Transgene Regulation.The Journal of biological chemistry · 2015Article
- Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells.Immunological reviews · 2014Review
- Adoptive T-cell therapy for Leukemia.Molecular and cellular therapies · 2014Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Genetic modification of human T cells to express transgene-encoded polypeptides, such as tumor targeting chimeric antigen receptors, is an emerging therapeutic modality showing promise in clinical trials. The development of simple and efficient techniques for purifying transgene(+) T cells is needed to facilitate the derivation of cell products with uniform potency and purity. Unlike selection platforms that utilize physical methods (immunomagnetic or sorting) that are technically cumbersome and limited by the expense and availability of clinical-grade components, we focused on designing a selection system on the basis of the pharmaceutical drug methotrexate (MTX), a potent allosteric inhibitor of human dihydrofolate reductase (DHFR). Here, we describe the development of self inactivating (SIN) lentiviral vectors that direct the coordinated expression of a CD19-specific chimeric antigen receptor (CAR), the human EGFRt tracking/suicide construct, and a methotrexate-resistant human DHFR mutein (huDHFR(FS); L22F, F31S). Our results demonstrate that huDHFR(FS) expression renders lentivirally transduced primary human CD45RO(+)CD62L(+) central memory T cells resistant to lymphotoxic concentrations of MTX up to 0.1 μM. Our modular complementary DNA (cDNA) design insures that selected MTX-resistant T cells co-express functionally relevant levels of the CD19-specific CAR and EGFRt. This selection system on the basis of huDHFR(FS) and MTX has considerable potential utility in the manufacturing of clinical-grade T cell products.
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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.