ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
Simultaneous Deletion of Endogenous TCRαβ for TCR Gene Therapy Creates an Improved and Safe Cellular Therapeutic.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 67 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
- The development of single-cell lineage tracing technology and its application in immunotherapy.Molecular therapy. Advances · 2026Review
- T cell receptors equipped with ICOS provide T cells with durable anti-tumor response.Molecular cancer · 2026Article
- T cell senescence and exhaustion: molecular mechanisms and immune rejuvenation for cancer immunotherapy.Signal transduction and targeted therapy · 2026Review
- The Role of Chimeric Antigen Receptor Regulatory T Cells in Promoting Immune Tolerance in Solid Organ Transplantation:Saudi medical journal · 2026Review
- A modular γδ TCR-T platform combining KRAS pMHC targeting with re-dosable mRNA engager redirection.Journal of hematology & oncology · 2026Article
- Strategies to eliminate native T cell receptors for adoptive T cell therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- A universal platform for simultaneous TCRα/β removal enables safer and more potent TCR therapies and autoimmune modeling.bioRxiv : the preprint server for biology · 2026Article
- CRISPR/Cas9 Technology for Modifying Immune Checkpoint in CAR-T Cell Therapy for Hematopoietic Malignancies.Current gene therapy · 2026Review
- From delivery to integration: CRISPR-mediated large insert gene editing in primary human T cells.Clinical & translational immunology · 2026Review
- CRISPR tools for T cells: targeting the genome, epigenome, and transcriptome.Trends in cancer · 2025Review
- Bioengineered T-cell therapies for precision immunotherapy in renal transplantation, autoimmune relapse, and sensitization.Clinical kidney journal · 2025Review
- An overview on in-vivo generation of CAR-T cells using CRISPR-loaded functionalized nanocarriers for treating B-cell lineage acute lymphoblastic leukemia.Molecular biology reports · 2025Review
- MutatedFrontiers in immunology · 2025Article
- A pooled CRISPR screen identifies the Tα2 enhancer element as a driver ofFrontiers in immunology · 2025Article
- CRISPR technology in human diseases.MedComm · 2024Review
- Identification of an HLA-A*11:01-restricted neoepitope of mutant PIK3CA and its specific T cell receptors for cancer immunotherapy targeting hotspot driver mutations.Cancer immunology, immunotherapy : CII · 2024Article
- The recent advancement of TCR-T cell therapies for cancer treatment.Acta biochimica et biophysica Sinica · 2024Review
- CRISPR-Cas9 applications in T cells and adoptive T cell therapies.Cellular & molecular biology letters · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Generation of an optimal T cell therapeutic expressing high frequencies of transgenic T cell receptor (tgTCR) is essential for improving TCR gene therapy. Upon TCR gene transfer, presence of endogenous TCRαβ reduces expression of tgTCR due to TCR mixed-dimer formation and competition for binding CD3. Knockout (KO) of endogenous TCRαβ was recently achieved using CRISPR/Cas9 editing of the TRAC or TRBC loci, resulting in increased expression and function of tgTCR. Here, we adopt this approach into current protocols for generating T cell populations expressing tgTCR to validate this strategy in the context of four clinically relevant TCRs. First, simultaneous editing of TRAC and TRBC loci was reproducible and resulted in high double KO efficiencies in bulk CD8 T cells. Next, tgTCR expression was significantly higher in double TRAC/BC KO conditions for all TCRs tested, including those that contained structural modifications to encourage preferential pairing. Finally, increased expression of tgTCR in edited T cell populations allowed for increased recognition of antigen expressing tumor targets and prolonged control of tumor outgrowth in a preclinical model of multiple myeloma. In conclusion, CRISPR/Cas9-mediated KO of both endogenous TCRαβ chains can be incorporated in current T cell production protocols and is preferential to ensure an improved and safe clinical therapeutic.
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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.