ArticleNature communications2019
Framework engineering to produce dominant T cell receptors with enhanced antigen-specific function.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
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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
44 citing papers in PubMed, 62 citations in OpenAlex.
- Computational design of optimized and preferentially paired human TCR constant regions for improved T cell function.Science advances · 2026Article
- A platform for parallel TCR cloning and testing enables anti-neoantigen tumor immunotherapy.JCI insight · 2026Article
- A multi-ethnic reference map of T cell receptor germline diversity reveals evidence of natural selection on alpha chain genes.Nature communications · 2026Article
- Engineering a Second Interchain Disulfide Bond in the αβ T-Cell Receptor Constant Domain: A Powerful Strategy to Enhance Stability, Pairing Fidelity, and Therapeutic Efficacy in TCR-T Cell Therapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- De novo engineered disulfide bond supersedes native interchain linkage to enhance TCR pairing and anti-tumor efficacy in T cell therapy.Cellular & molecular immunology · 2026Article
- Article
- High-throughput cloning reveals diverse properties of T-cell receptors targeting minor histocompatibility antigens.Blood advances · 2026Article
- LANA-specific CD4Nature communications · 2025Article
- Engineering innate immune cells for cancer immunotherapy.Nature biotechnology · 2025Review
- Rapid parallel reconstruction and specificity screening of hundreds of T cell receptors.Nature protocols · 2025Review
- Adoptive cell therapy for cancer: combination strategies and biomarkers.Frontiers in immunology · 2025Review
- TCR-Engineered T Cells Directed against Ropporin-1 Constitute a Safe and Effective Treatment for Triple-Negative Breast Cancer.Cancer discovery · 2024Article
- Rational Protein Engineering to Enhance MHC-Independent T-cell Receptors.Cancer discovery · 2024Article
- Applications of cell therapy in the treatment of virus-associated cancers.Nature reviews. Clinical oncology · 2024Review
- Focusing on CD8Journal of experimental & clinical cancer research : CR · 2024Review
- Review
- Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.Experimental hematology & oncology · 2024Review
- Exploitation of CD3ζ to enhance TCR expression levels and antigen-specific T cell function.Frontiers in immunology · 2024Article
- T cell receptor therapeutics: immunological targeting of the intracellular cancer proteome.Nature reviews. Drug discovery · 2023Review
- Challenges and solutions for therapeutic TCR-based agents.Immunological reviews · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
TCR-gene-transfer is an efficient strategy to produce therapeutic T cells of defined antigen specificity. However, there are substantial variations in the cell surface expression levels of human TCRs, which can impair the function of engineered T cells. Here we demonstrate that substitutions of 3 amino acid residues in the framework of the TCR variable domains consistently increase the expression of human TCRs on the surface of engineered T cells.The modified TCRs mediate enhanced T cell proliferation, cytokine production and cytotoxicity, while reducing the peptide concentration required for triggering effector function up to 3000-fold. Adoptive transfer experiments in mice show that modified TCRs control tumor growth more efficiently than wild-type TCRs. Our data indicate that simple variable domain modifications at a distance from the antigen-binding loops lead to increased TCR expression and improved effector function. This finding provides a generic platform to optimize the efficacy of TCR gene therapy in humans.
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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.