ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Specific increase in potency via structure-based design of a TCR.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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
34 citing papers in PubMed, 44 citations in OpenAlex.
- Structural T-Cell Receptor Analysis in the Age of Machine Learning.Immunological reviews · 2026Review
- In situ cell-surface conformation of the TCR-CD3 signaling complex.EMBO reports · 2024Article
- Strategies and rules for tuning TCR-derived therapy.Expert reviews in molecular medicine · 2023Review
- TCRmodel2: high-resolution modeling of T cell receptor recognition using deep learning.Nucleic acids research · 2023Article
- Structural analysis of cancer-relevant TCR-CD3 and peptide-MHC complexes by cryoEM.Nature communications · 2023Article
- TCR-engineered T cell therapy in solid tumors: State of the art and perspectives.Science advances · 2023Review
- Structural insights into engineering a T-cell receptor targeting MAGE-A10 with higher affinity and specificity for cancer immunotherapy.Journal for immunotherapy of cancer · 2022Article
- Engineering the T cell receptor for fun and profit: Uncovering complex biology, interrogating the immune system, and targeting disease.Current opinion in structural biology · 2022Review
- Engineering soluble T-cell receptors for therapy.The FEBS journal · 2021Review
- An HLA-A*11:01-Binding Neoantigen from Mutated NPM1 as Target for TCR Gene Therapy in AML.Cancers · 2021Article
- Molecular design of the γδT cell receptor ectodomain encodes biologically fit ligand recognition in the absence of mechanosensing.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Constant regulation for stable CD8 T-cell functional avidity and its possible implications for cancer immunotherapy.European journal of immunology · 2021Review
- Gene Augmentation and Editing to Improve TCR Engineered T Cell Therapy against Solid Tumors.Vaccines · 2020Review
- Review
- T-cell receptor affinity in the age of cancer immunotherapy.Molecular carcinogenesis · 2020Review
- Adoptive T cell therapy: Boosting the immune system to fight cancer.Seminars in immunology · 2020Review
- Predicting Cross-Reactivity and Antigen Specificity of T Cell Receptors.Frontiers in immunology · 2020Review
- Empirical and Rational Design of T Cell Receptor-Based Immunotherapies.Frontiers in immunology · 2020Review
- Understanding TCR affinity, antigen specificity, and cross-reactivity to improve TCR gene-modified T cells for cancer immunotherapy.Cancer immunology, immunotherapy : CII · 2019Review
- Improving T Cell Receptor On-Target Specificity via Structure-Guided Design.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Adoptive immunotherapy with Ag-specific T lymphocytes is a powerful strategy for cancer treatment. However, most tumor Ags are nonreactive "self" proteins, which presents an immunotherapy design challenge. Recent studies have shown that tumor-specific TCRs can be transduced into normal PBLs, which persist after transfer in ∼30% of patients and effectively destroy tumor cells in vivo. Although encouraging, the limited clinical responses underscore the need for enrichment of T cells with desirable antitumor capabilities prior to patient transfer. In this study, we used structure-based design to predict point mutations of a TCR (DMF5) that enhance its binding affinity for an agonist tumor Ag-MHC (peptide-MHC [pMHC]), Mart-1 (27L)-HLA-A2, which elicits full T cell activation to trigger immune responses. We analyzed the effects of selected TCR point mutations on T cell activation potency and analyzed cross-reactivity with related Ags. Our results showed that the mutated TCRs had improved T cell activation potency while retaining a high degree of specificity. Such affinity-optimized TCRs have demonstrated to be very specific for Mart-1 (27L), the epitope for which they were structurally designed. Although of somewhat limited clinical relevance, these studies open the possibility for future structural-based studies that could potentially be used in adoptive immunotherapy to treat melanoma while avoiding adverse autoimmunity-derived effects.
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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.