ArticleNature biotechnology2017
Generation of higher affinity T cell receptors by antigen-driven differentiation of progenitor T cells in vitro.
Article in Nature biotechnology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- The immune system of preterm infants: an overview.Frontiers in immunology · 2026Review
- Focusing on CD8Journal of experimental & clinical cancer research : CR · 2024Review
- Exploring the potential of structure-based deep learning approaches for T cell receptor design.PLoS computational biology · 2024Article
- Expansion of the HSV-2-specific T cell repertoire in skin after immunotherapeutic HSV-2 vaccine.JCI insight · 2024Article
- Exploring the Potential of Structure-Based Deep Learning Approaches for T cell Receptor Design.bioRxiv : the preprint server for biology · 2024Article
- Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.Experimental hematology & oncology · 2024Review
- Repeated mRNA vaccination sequentially boosts SARS-CoV-2-specific CD8Nature immunology · 2024Article
- CD8Research square · 2022Article
- TCR signal strength defines distinct mechanisms of T cell dysfunction and cancer evasion.The Journal of experimental medicine · 2022Article
- Systematic Pan-Cancer Analysis Identifies CDK1 as an Immunological and Prognostic Biomarker.Journal of oncology · 2022Article
- Competition-Based Cell Assay Employing Soluble T Cell Receptors to Assess MHC Class II Antigen Processing and Presentation.The AAPS journal · 2021Article
- Tissue-Resident-Memory CD8Frontiers in immunology · 2021Article
- Review
- Review
- Cancer testis antigen Cyclin A1 harbors several HLA-A*02:01-restricted T cell epitopes, which are presented and recognized in vivo.Cancer immunology, immunotherapy : CII · 2020Article
- T-cell receptor affinity in the age of cancer immunotherapy.Molecular carcinogenesis · 2020Review
- Antigen Experienced T Cells from Peripheral Blood Recognize p53 Neoantigens.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Anti-BCMA chimeric antigen receptors with fully human heavy-chain-only antigen recognition domains.Nature communications · 2020Article
- TCR Redirected T Cells for Cancer Treatment: Achievements, Hurdles, and Goals.Frontiers in immunology · 2020Review
- Computational Prediction and Validation of Tumor-Associated Neoantigens.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Many promising targets for T-cell-based cancer immunotherapies are self-antigens. During thymic selection, T cells bearing T cell receptors (TCRs) with high affinity for self-antigen are eliminated. The affinity of the remaining low-avidity TCRs can be improved to increase their antitumor efficacy, but conventional saturation mutagenesis approaches are labor intensive, and the resulting TCRs may be cross-reactive. Here we describe the in vitro maturation and selection of mouse and human T cells on antigen-expressing feeder cells to develop higher-affinity TCRs. The approach takes advantage of natural Tcrb gene rearrangement to generate diversity in the length and composition of CDR3β. In vitro differentiation of progenitors transduced with a known Tcra gene in the presence of antigen drives differentiation of cells with a distinct agonist-selected phenotype. We purified these cells to generate TCRβ chain libraries pre-enriched for target antigen specificity. Several TCRβ chains paired with a transgenic TCRα chain to produce a TCR with higher affinity than the parental TCR for target antigen, without evidence of cross-reactivity.
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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.