ArticleScientific reports2020
Abrogation of HLA surface expression using CRISPR/Cas9 genome editing: a step toward universal T cell therapy.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 51 citations in OpenAlex.
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- Glycan-encoded immune checkpoints and allorecognition: a mechanistic framework for transplantation and organ engineering.Frontiers in transplantation · 2026Review
- Regulatory T cell therapies: biological foundations, engineering strategies, and clinical translation.Frontiers in immunology · 2026Review
- Article
- Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.Journal of hematology & oncology · 2025Review
- CRISPR tools for T cells: targeting the genome, epigenome, and transcriptome.Trends in cancer · 2025Review
- A Novel Early Memory-Enriched Allogeneic NKG2D CAR-T Cell Therapy Based on CRISPR/Cas9 Technology for Solid Tumors.Cancers · 2025Article
- [Advances in the application strategies of CRISPR/Cas9 technology in chimeric antigen receptor T cell therapy for hematological malignancies].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Review
- Molecular advances in transfusion medicine: a narrative review.Frontiers in medicine · 2025Review
- New frontiers in retinal transplantation.World journal of transplantation · 2024Review
- Progress in Organ Bioprinting for Regenerative Medicine.Engineering (Beijing, China) · 2024Article
- Immunosuppressant therapy averts rejection of allogeneic FKBP1A-disrupted CAR-T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Viral and nonviral nanocarriers forNano research · 2024Article
- Engineering immune-evasive allogeneic cellular immunotherapies.Nature reviews. Immunology · 2024Review
- HLA reduction of human T cells facilitates generation of immunologically multicompatible cellular products.Blood advances · 2024Article
- Stealth transgenes enable CAR-T cells to evade host immune responses.Journal for immunotherapy of cancer · 2024Article
- High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models.Cancer immunology research · 2024Article
- Allogeneic CAR-T cells with of HLA-A/B and TRAC disruption exhibit promising antitumor capacity against B cell malignancies.Cancer immunology, immunotherapy : CII · 2024Article
- Generating universal anti-CD19 CAR T cells with a defined memory phenotype by CRISPR/Cas9 editing and safety evaluation of the transcriptome.Frontiers in immunology · 2024Article
- Cyclosporine A-resistant CAR-T cells mediate antitumour immunity in the presence of allogeneic cells.Nature communications · 2023Article
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
As recent advancements in the chimeric antigen receptor-T cells have revolutionized the way blood cancers are handled, potential benefits from producing off-the-shelf, standardized immune cells entail the need for development of allogeneic immune cell therapy. However, host rejection driven by HLA disparity in adoptively transferred allogeneic T cells remains a key obstacle to the universal donor T cell therapy. To evade donor HLA-mediated immune rejection, we attempted to eliminate T cell's HLA through the CRISPR/Cas9 gene editing system. First, we screened 60 gRNAs targeting B2M and multiple sets of gRNA each targeting α chains of HLA-II (DPA, DQA and DRA, respectively) using web-based design tools, and identified specific gRNA sequences highly efficient for target deletion without carrying off-target effects. Multiplex genome editing of primary human T cells achieved by the newly discovered gRNAs yielded HLA-I- or HLA-I/II-deficient T cells that were phenotypically unaltered and functionally intact. The overnight mixed lymphocyte reactions demonstrated the HLA-I-negative cells induced decreased production of IFN-γ and TNF-α in alloreactive T cells, and deficiency of HLA-I/II in T cells further dampened the inflammatory responses. Taken together, our approach will provide an efficacious pathway toward the universal donor cell generation by manipulating HLA expression in therapeutic T cells.
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