ArticleGene therapy2013
Design of T-cell receptor libraries with diverse binding properties to examine adoptive T-cell responses.
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 17 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.
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Who cites it
17 citing papers in PubMed, 19 citations in OpenAlex.
- TCR catch bonds nonlinearly control CD8 cooperation to shape T cell specificity.Cell research · 2025Article
- Factors contributing to the potency of CD8Trends in immunology · 2023Review
- Article
- Engineering of an Avidity-Optimized CD19-Specific Parallel Chimeric Antigen Receptor That Delivers Dual CD28 and 4-1BB Co-Stimulation.Frontiers in immunology · 2022Article
- Why the Outcome of Anti-Tumor Immune Responses is Heterogeneous: A Novel Idea in the Context of Immunological Heterogeneity in Cancers.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Article
- Human leucocyte antigen class I-redirected anti-tumour CD4Clinical and experimental immunology · 2017Article
- More or less-On the influence of labelling strategies to infer cell population dynamics.PloS one · 2017Article
- Cish actively silences TCR signaling in CD8+ T cells to maintain tumor tolerance.The Journal of experimental medicine · 2015Article
- Tuning Sensitivity of CAR to EGFR Density Limits Recognition of Normal Tissue While Maintaining Potent Antitumor Activity.Cancer research · 2015Article
- T cell receptor binding affinity governs the functional profile of cancer-specific CD8+ T cells.Clinical and experimental immunology · 2015Article
- TCR affinity for p/MHC formed by tumor antigens that are self-proteins: impact on efficacy and toxicity.Current opinion in immunology · 2015Review
- Identifying Individual T Cell Receptors of Optimal Avidity for Tumor Antigens.Frontiers in immunology · 2015Review
- T Cell Receptor Engineering and Analysis Using the Yeast Display Platform.Methods in molecular biology (Clifton, N.J.) · 2015Article
- A novel T cell receptor single-chain signaling complex mediates antigen-specific T cell activity and tumor control.Cancer immunology, immunotherapy : CII · 2014Article
- Plasticity in the contribution of T cell receptor variable region residues to binding of peptide-HLA-A2 complexes.Journal of molecular biology · 2013Article
- Transnuclear TRP1-specific CD8 T cells with high or low affinity TCRs show equivalent antitumor activity.Cancer immunology research · 2013Article
- Role of T cell receptor affinity in the efficacy and specificity of adoptive T cell therapies.Frontiers in immunology · 2013Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Adoptive T-cell therapies have shown significant promise in the treatment of cancer and viral diseases. One approach, which introduces antigen-specific T-cell receptors (TCRs) into ex vivo activated T cells, is designed to overcome central tolerance mechanisms that prevent responses by endogenous T-cell repertoires. Studies have suggested that use of higher-affinity TCRs against class I major histocompatibility complex antigens could drive the activity of both CD4(+) and CD8(+) T cells, but the rules that govern the TCR binding optimal for in vivo activity are unknown. Here, we describe a high-throughput platform of 'reverse biochemistry' whereby a library of TCRs with a wide range of binding properties to the same antigen is introduced into T cells and adoptively transferred into mice with antigen-positive tumors. Extraction of RNA from tumor-infiltrating lymphocytes (TILs) or lymphoid organs allowed high-throughput sequencing to determine which TCRs were selected in vivo. The results showed that CD8(+) T cells expressing the highest-affinity TCR variants were deleted in both the TIL population and in peripheral lymphoid tissues. In contrast, these same high-affinity TCR variants were preferentially expressed within CD4(+) T cells in the tumor, suggesting they had a role in antigen-specific tumor control. The findings thus revealed that the affinity of the transduced TCRs controlled the survival and tumor infiltration of the transferred T cells. Accordingly, the TCR library strategy enables rapid assessment of TCR-binding properties that promote peripheral T-cell survival and tumor elimination.
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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.