ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
CRISPR-Cas9-Mediated Glucocorticoid Resistance in Virus-Specific T Cells for Adoptive T Cell Therapy Posttransplantation.
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 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- CMV-specific T-cell receptor-engineered T-cell therapy as first-line treatment for CMV reactivation after haploidentical hematopoietic stem cell transplantation: a phase 2 trial.Frontiers in immunology · 2026Trial
- Next-generation LMP2A-targeting TCR-recombinant T cells with inducible IL-18 expression to treat EBV-associated malignancies.Molecular therapy. Oncology · 2026Article
- Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review.Pathogens (Basel, Switzerland) · 2025Article
- Steroid hormones as modulators of anti-tumoural immunity.Nature reviews. Endocrinology · 2025Review
- Treating Adenovirus Infection in Transplant Populations: Therapeutic Options Beyond Cidofovir?Viruses · 2025Review
- All-in-one CRISPR/Cas-engineered glucocorticoid-receptor knock-out EBV-gp350-CAR knock-in T cells are potent and resistant to dexamethasone.Experimental hematology & oncology · 2025Article
- Gene editing of CD3 epsilon to redirect regulatory T cells for adoptive T cell transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Prophylactic VSTs: a promising start but still work to do.Blood advances · 2024Article
- Engineering immune-evasive allogeneic cellular immunotherapies.Nature reviews. Immunology · 2024Review
- Transplant international : official journal of the European Society for Organ Transplantation · 2024Article
- Pathogen-specific T Cells: Targeting Old Enemies and New Invaders in Transplantation and Beyond.HemaSphere · 2023Review
- Protective T cell receptor identification for orthotopic reprogramming of immunity in refractory virus infections.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Genome-wide off-target analyses of CRISPR/Cas9-mediated T-cell receptor engineering in primary human T cells.Clinical & translational immunology · 2022Article
- Regulatory T Cell Therapy of Graft-versus-Host Disease: Advances and Challenges.International journal of molecular sciences · 2021Review
- Immunotherapy with adoptive cytomegalovirus-specific T cells transfer: Summarizing latest gene engineering techniques.Health science reports · 2021Review
- Reinforcing the Immunocompromised Host Defense against Fungi: Progress beyond the Current State of the Art.Journal of fungi (Basel, Switzerland) · 2021Review
- CRISPR-Cas9-Edited Tacrolimus-Resistant Antiviral T Cells for Advanced Adoptive Immunotherapy in Transplant Recipients.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Super-Treg: Toward a New Era of Adoptive Treg Therapy Enabled by Genetic Modifications.Frontiers in immunology · 2020Review
- "Cerberus" T Cells: A Glucocorticoid-Resistant, Multi-Pathogen Specific T Cell Product to Fight Infections in Severely Immunocompromised Patients.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunosuppression posttransplantation exposes patients to an increased risk for refractory viral infections as an important cause of morbidity and mortality. Protective T cell immunity can be restored by adoptive T cell transfer, but ongoing immunosuppression limits efficacy of T cell responses. In order to deliver protection against viral pathogens and allow at the same time necessary steroid therapy, we generated glucocorticoid-resistant T cells by CRISPR-Cas9-mediated knockout of the glucocorticoid receptor in primary human virus-specific T cell products. Characterization of the T cell product revealed high efficiency of glucocorticoid receptor knockout and high purity of virus-specific T cells. This tandem T cell engineering preserved protective T cell functionality, such as cytotoxicity, CD107a degranulation, proliferative capacity, and cytokine release patterns. Virus-specific T cells with glucocorticoid receptor knockout were resistant to the suppressive effect of dexamethasone treatment on lymphocyte proliferation and cytokine secretion (tumor necrosis factor alpha [TNF-α], interleukin-4 [IL-4], IL-6, and sFas). Additionally, glucocorticoid receptor knockout cells remained sensitive to cyclosporine A treatment, thereby providing a rescue approach for patients in case of safety issues. This novel approach provides a therapeutic option for the treatment of patients with viral infections after transplantation who are receiving glucocorticoid therapy.
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