ArticleExperimental hematology & oncology2023
CRISPR/Cas9-mediated knockout of intracellular molecule SHP-1 enhances tumor-killing ability of CD133-targeted CAR T cells in vitro.
Article in Experimental hematology & oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Recent Advances in Research on SHP Family Phosphatases: Signal Regulation Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- PTPN6/SHP-1 in autoimmune disease: immune tolerance, regulatory mechanisms, and therapeutic targeting.Frontiers in immunology · 2026Review
- Adoptive T Cell therapy for cancer and autoimmune disease: current advances, challenges, and future directions.Oncology reviews · 2026Article
- CD5 ablation enhances persistence and antitumor potency of engineered T cells by mitigating exhaustion and promoting cytotoxicity.Journal for immunotherapy of cancer · 2025Article
- Challenges and strategies in clinical applications of CAR-T therapy for autoimmune diseases.Journal of hematology & oncology · 2025Review
- Challenges and perspectives of CAR-T cell therapy in solid tumours: insights from gastric cancer.British journal of cancer · 2025Review
- Fine tuning towards the next generation of engineered T cells.Nature biomedical engineering · 2025Review
- Recent advances and challenges of cellular immunotherapies in lung cancer treatment.Experimental hematology & oncology · 2025Review
- CRISPR/Cas9-mediated SHP-1-knockout T cells combined with simvastatin enhances anti-tumor activity in humanized-PDX HCC model.iScience · 2025Article
- Engineering the next generation of CAR T- cells: precision modifications, logic gates and universal strategies to overcome exhaustion and tumor resistance.Frontiers in oncology · 2025Review
- CAR T-cell therapy in autoimmune diseases: a promising frontier on the horizon.Frontiers in immunology · 2025Review
- Global research trends in CAR-T cell therapy for solid tumors: A comprehensive visualization and bibliometric study (2012-2023).Human vaccines & immunotherapeutics · 2024Article
- A bibliometric and knowledge-map study on the treatment of hematological malignancies with CAR-T cells from 2012 to 2023.Human vaccines & immunotherapeutics · 2024Article
- Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies.Journal of hematology & oncology · 2024Review
- CRISPR-Cas9 applications in T cells and adoptive T cell therapies.Cellular & molecular biology letters · 2024Review
- Identification of genetic modifiers enhancing B7-H3-targeting CAR T cell therapy against glioblastoma through large-scale CRISPRi screening.Journal of experimental & clinical cancer research : CR · 2024Article
- Transcriptomics analysis of LINC02202/XBP1 axis in melanoma: Implications for drug targeting and PD-1 monoclonal antibody efficacy.Journal of cellular and molecular medicine · 2024Article
- Review
- Revolutionizing cancer treatment: enhancing CAR-T cell therapy with CRISPR/Cas9 gene editing technology.Frontiers in immunology · 2024Review
- Consideration of SHP-1 as a Molecular Target for Tumor Therapy.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 2 countries.
Funding
Abstract
CAR T cell therapy has been successfully used in the treatment of hematological malignancies, and the strategy that deletion of inhibitory receptor on the CAR T cell surface, such as PD-1, greatly enhance the antitumor effects. Here, we describe a one-step electroporation for the co-transfection of Cas9:sgRNA and CAR plasmids on primary T cells to demonstrate the effect of SHP-1 deletion in CAR T cells. By using PiggyBac Transposase system, we can achieve more than 90% of T cells express CAR gene and nearly 60% SHP-1 knockout efficiency in T cells. We show that knockout of SHP-1 in CD133 CAR T cells resulted in significantly improve the cytolysis effect on CD133 positive glioma cell lines. We further demonstrate that the enhanced antitumor efficacy of SHP-1 deletion is due to the increased release of TNF-α, IL-2 and IFN-γ in vitro. Finally, we evaluated the biosafety of Cas9 genome editing and did not find any insertions of Cas9 and obvious editing in off-target sites in CAR T cells. These data provide an approach for achieving both intracellular inhibitory molecule, SHP-1 deletion and CD133 CAR gene over-expression in human T cells. And SHP-1 could be a new potential target for adoptive CAR T cells immunotherapy.
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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.