ArticleInternational journal of molecular sciences2022
Preclinical Evaluation of CRISPR-Edited CAR-NK-92 Cells for Off-the-Shelf Treatment of AML and B-ALL.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 48 citations in OpenAlex.
- Next-generation CAR-NK cell therapy: engineering strategies, translational challenges, and future perspectives in cancer immunotherapy.Cancer cell international · 2026Review
- CAR-NK cell therapy for hematologic malignancies: advances, challenges and optimization strategies.Molecular cancer · 2026Review
- Defining the role of natural killer cells in acute myeloid leukemia through the lens of single-cell omics.Frontiers in immunology · 2026Review
- Overcoming barriers in CAR-NK immunotherapy: CRISPR-Driven advances in checkpoint editing and allogeneic design.Functional & integrative genomics · 2025Review
- Review
- CAR-T and CAR-NK cell therapies in AML: breaking barriers and charting the future.Journal of translational medicine · 2025Review
- Induced Pluripotent Stem Cell-Based Cancer Immunotherapy: Strategies and Perspectives.Biomedicines · 2025Review
- Actionable heterogeneity of hepatocellular carcinoma therapy-induced senescence.Cancer immunology, immunotherapy : CII · 2025Article
- GD2-CAR NK-92 cell activity against neuroblastoma cells is insusceptible to TIGIT knockout.Cancer immunology, immunotherapy : CII · 2025Article
- Revolutionising Cancer Immunotherapy: Advancements and Prospects in Non-Viral CAR-NK Cell Engineering.Cell proliferation · 2025Review
- TIGIT/PVR axis regulates anti-tumor immunity in hematologic malignancies.Annals of hematology · 2025Review
- Empowering Natural Killer Cells to Combat Acute Myeloid Leukemia: Perspective on CAR-NK Cell Therapy.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Review
- NK cell function down regulated by HMGB2 through ANGPT1/PI3K/AKT pathway and its effect on esophageal squamous carcinoma cells.Frontiers in immunology · 2025Article
- Engineering with care: safety assessment platforms for CRISPR-modified natural killer cells.Frontiers in immunology · 2025Review
- CAR-NK cells: harnessing the power of natural killers for advanced cancer therapy.Frontiers in immunology · 2025Review
- CAR-NK cell for gynecological cancers: immune microenvironment remodeling and immunotherapeutic strategies.Frontiers in immunology · 2025Review
- Senescent T Cells: The Silent Culprit in Acute Myeloid Leukemia Progression?International journal of molecular sciences · 2024Review
- CAR-NK cells for gastrointestinal cancer immunotherapy: from bench to bedside.Molecular cancer · 2024Review
- Beyond CAR-T: The rise of CAR-NK cell therapy in asthma immunotherapy.Journal of translational medicine · 2024Review
- CRISPR technology in human diseases.MedComm · 2024Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Acute myeloid leukemia (AML) and B-cell acute lymphocytic leukemia (B-ALL) are severe blood malignancies affecting both adults and children. Chimeric antigen receptor (CAR)-based immunotherapies have proven highly efficacious in the treatment of leukemia. However, the challenge of the immune escape of cancer cells remains. The development of more affordable and ready-to-use therapies is essential in view of the costly and time-consuming preparation of primary cell-based treatments. In order to promote the antitumor function against AML and B-ALL, we transduced NK-92 cells with CD276-CAR or CD19-CAR constructs. We also attempted to enhance cytotoxicity by a gene knockout of three different inhibitory checkpoints in NK cell function (CBLB, NKG2A, TIGIT) with CRISPR-Cas9 technology. The antileukemic activity of the generated cell lines was tested with calcein and luciferase-based cytotoxicity assays in various leukemia cell lines. Both CAR-NK-92 exhibited targeted cytotoxicity and a significant boost in antileukemic function in comparison to parental NK-92. CRISPR-Cas9 knock-outs did not improve B-ALL cytotoxicity. However, triple knock-out CD276-CAR-NK-92 cells, as well as CBLB or TIGIT knock-out NK-92 cells, showed significantly enhanced cytotoxicity against U-937 or U-937 CD19/tag AML cell lines. These results indicate that the CD19-CAR and CD276-CAR-NK-92 cell lines' cytotoxic performance is suitable for leukemia killing, making them promising off-the-shelf therapeutic candidates. The knock-out of CBLB and TIGIT in NK-92 and CD276-CAR-NK-92 should be further investigated for the treatment of AML.
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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.