ArticleClinical and experimental immunology2015
T cell receptor binding affinity governs the functional profile of cancer-specific CD8+ T cells.
Article in Clinical and experimental immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- The Emerging World of TCR-T Cell Trials Against Cancer: A Systematic Review.Technology in cancer research & treatment · 2019Pooled it
- PD-1Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Renaissance of antiviral CD8Nature reviews. Immunology · 2026Review
- Pre-existing activation states shape functional heterogeneity of human Vγ9Vδ2 T cells.Frontiers in immunology · 2026Article
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.Frontiers in immunology · 2026Article
- AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2026Article
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.bioRxiv : the preprint server for biology · 2025Article
- Anti-PD-L2 immunotherapy is efficacious against melanoma in aged hosts through IL-17 and IFNγ signalling.Nature communications · 2025Article
- Review
- Phage display enables machine learning discovery of cancer antigen-specific TCRs.Science advances · 2025Article
- MHC-related protein 1-restricted recognition of cancer via a semi-invariant TCR-α chain.The Journal of clinical investigation · 2025Article
- SynNotch CAR-T cell, when synthetic biology and immunology meet again.Frontiers in immunology · 2025Review
- HLA A*24:02-restricted T cell receptors cross-recognize bacterial and preproinsulin peptides in type 1 diabetes.The Journal of clinical investigation · 2024Article
- Exploring the potential of structure-based deep learning approaches for T cell receptor design.PLoS computational biology · 2024Article
- Oxidized Melanoma Antigens Promote Activation and Proliferation of Cytotoxic T-Cell Subpopulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Identification and affinity enhancement of T-cell receptor targeting a KRASCommunications biology · 2024Article
- Exploring the Potential of Structure-Based Deep Learning Approaches for T cell Receptor Design.bioRxiv : the preprint server for biology · 2024Article
- Discrete class I molecules on brain endothelium differentially regulate neuropathology in experimental cerebral malaria.Brain : a journal of neurology · 2024Article
- Distinct T cell polyfunctional profile in SARS-CoV-2 seronegative children associated with endemic human coronavirus cross-reactivity.iScience · 2024Article
- Selection, engineering, and in vivo testing of a human leukocyte antigen-independent T-cell receptor recognizing human mesothelin.PloS one · 2024Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Antigen-specific T cell receptor (TCR) gene transfer via patient-derived T cells is an attractive approach to cancer therapy, with the potential to circumvent immune regulatory networks. However, high-affinity tumour-specific TCR clonotypes are typically deleted from the available repertoire during thymic selection because the vast majority of targeted epitopes are derived from autologous proteins. This process places intrinsic constraints on the efficacy of T cell-based cancer vaccines and therapeutic strategies that employ naturally generated tumour-specific TCRs. In this study, we used altered peptide ligands and lentivirus-mediated transduction of affinity-enhanced TCRs selected by phage display to study the functional properties of CD8(+) T cells specific for three different tumour-associated peptide antigens across a range of binding parameters. The key findings were: (i) TCR affinity controls T cell antigen sensitivity and polyfunctionality; (ii) supraphysiological affinity thresholds exist, above which T cell function cannot be improved; and (iii) T cells transduced with very high-affinity TCRs exhibit cross-reactivity with self-derived peptides presented by the restricting human leucocyte antigen. Optimal system-defined affinity windows above the range established for natural tumour-specific TCRs therefore allow the enhancement of T cell effector function without off-target effects. These findings have major implications for the rational design of novel TCR-based biologics underpinned by rigorous preclinical evaluation.
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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.