ArticleGene therapy2012
Single-chain VαVβ T-cell receptors function without mispairing with endogenous TCR chains.
Article in Gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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.
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Who cites it
39 citing papers in PubMed, 55 citations in OpenAlex.
- The evolution of cellular therapies in sarcoma: Breakthroughs, challenges, and future directions.Human vaccines & immunotherapeutics · 2026Review
- Computational design of optimized and preferentially paired human TCR constant regions for improved T cell function.Science advances · 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
- Strategies to eliminate native T cell receptors for adoptive T cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Modifications to rhesus macaque TCR constant regions improve TCR cell surface expression.PloS one · 2025Article
- Harnessing antibody-mediated recognition of the intracellular proteome with T cell receptor-like specificity.Frontiers in immunology · 2024Review
- Current and future concepts for the generation and application of genetically engineered CAR-T and TCR-T cells.Frontiers in immunology · 2023Review
- Modifications outside CDR1, 2 and 3 of the TCR variable β domain increase TCR expression and antigen-specific function.Frontiers in immunology · 2023Article
- The Intracellular Proteome as a Source for Novel Targets in CAR-T and T-Cell Engagers-Based Immunotherapy.Cells · 2022Review
- Rapid screening of TCR-pMHC interactions by the YAMTAD system.Cell discovery · 2022Article
- Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects.Frontiers in immunology · 2022Review
- Emerging Strategies in TCR-Engineered T Cells.Frontiers in immunology · 2022Review
- Adoptive T-cell Immunotherapy: Perfecting Self-Defenses.Experientia supplementum (2012) · 2022Article
- Novel TCR-like CAR-T cells targeting an HLA∗0201-restricted SSX2 epitope display strong activity against acute myeloid leukemia.Molecular therapy. Methods & clinical development · 2021Article
- Evolution of CD8Cells · 2021Review
- Adoptive Immunotherapy beyond CAR T-Cells.Cancers · 2021Review
- CRISPR/Cas9 Gene-Editing in Cancer Immunotherapy: Promoting the Present Revolution in Cancer Therapy and Exploring More.Frontiers in cell and developmental biology · 2021Review
- TCR-T Immunotherapy: The Challenges and Solutions.Frontiers in oncology · 2021Review
- CD4 Inhibits Helper T Cell Activation at Lower Affinity Threshold for Full-Length T Cell Receptors Than Single Chain Signaling Constructs.Frontiers in immunology · 2020Article
- Transgenic T-cell receptor immunotherapy for cancer: building on clinical success.Therapeutic advances in vaccines and immunotherapy · 2020Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Transduction of exogenous T-cell receptor (TCR) genes into patients' activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These 'mixed' heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not eliminate the formation of mixed heterodimers. By contrast, deletion of the constant regions, through use of a stabilized Vα/Vβ single-chain TCR (scTv), avoided mispairing completely. By linking a high-affinity scTv to intracellular signaling domains, such as Lck and CD28, the scTv was capable of activating functional T-cell responses in the absence of either the CD3 subunits or the co-receptors, and circumvented mispairing with endogenous TCRs. Such transduced T cells can respond to the targeted antigen independent of CD3 subunits via the introduced scTv, without the transduced T cells acquiring any new undefined and potentially dangerous specificities.
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What OpenQuestion holds
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.