ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
RNAi-mediated TCR knockdown prevents autoimmunity in mice caused by mixed TCR dimers following TCR gene transfer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 68 citations in OpenAlex.
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- Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.Journal of hematology & oncology · 2025Review
- Clinical development of allogeneic chimeric antigen receptor αβ-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Novel insights into TCR-T cell therapy in solid neoplasms: optimizing adoptive immunotherapy.Experimental hematology & oncology · 2024Review
- Allogeneic CAR-T cells for cancer immunotherapy.Immunotherapy · 2024Review
- Chimeric antigen receptors enable superior control of HIV replication by rapidly killing infected cells.PLoS pathogens · 2023Article
- Selection of highly responsive T cell receptors by an analysis combining the expression of multiple markers.Cancer science · 2023Article
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- Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond.HemaSphere · 2023Review
- EBAG9 silencing exerts an immune checkpoint function without aggravating adverse effects.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- A Novel Gene Controls a New Structure: PiggyBac Transposable Element-Derived 1, Unique to Mammals, Controls Mammal-Specific Neuronal Paraspeckles.Molecular biology and evolution · 2022Article
- siRNA-based nanotherapeutics as emerging modalities for immune-mediated diseases: A preliminary review.Cell biology international · 2022Review
- Antigen receptor-engineered Tregs inhibit CNS autoimmunity in cell therapy using nonredundant immune mechanisms in mice.European journal of immunology · 2022Article
- Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing.Nature communications · 2022Article
- TCR engineered T cells for solid tumor immunotherapy.Experimental hematology & oncology · 2022Review
- Donor T cells for CAR T cell therapy.Biomarker research · 2022Review
- Emerging Strategies in TCR-Engineered T Cells.Frontiers in immunology · 2022Review
- Rapid identification of CMV-specific TCRs via reverse TCR cloning system based on bulk TCR repertoire data.Frontiers in immunology · 2022Article
- Adoptive T-cell Immunotherapy: Perfecting Self-Defenses.Experientia supplementum (2012) · 2022Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetically modified T cells that express a transduced T cell receptor (TCR) α/β heterodimer in addition to their endogenous TCR are used in clinical studies to treat cancer. These cells express two TCR-α and two TCR-β chains that do not only compete for CD3 proteins but also form potentially self-reactive mixed TCR dimers, composed of endogenous and transferred chains. To overcome these deficits, we developed an RNAi-TCR replacement vector that simultaneously silences the endogenous TCR and expresses an RNAi-resistant TCR. Transduction of the virus-specific P14 TCR without RNAi resulted in unequal P14 TCR-α and -β chain surface levels, indicating heterodimerization with endogenous TCR chains. Such unequal expression was also observed following TCR gene optimization. Equal surface levels of the introduced TCR chains were however achieved by silencing the endogenous TCR. Importantly, all mice that received cells transduced with the native or optimized P14 TCR developed lethal TCR gene transfer-induced graft-versus-host-disease (TI-GVHD) due to formation of mixed TCR dimers. In contrast, TI-GVHD was almost completely prevented when using the RNAi-TCR replacement vector. Our data demonstrate that RNAi-assisted TCR replacement reduces the formation of mixed TCR dimers, and thereby significantly reduces the risk of TI-GVHD in TCR gene therapy.
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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.