ArticleFrontiers in immunology2024
Hypoimmunogenic CD19 CAR-NK cells derived from embryonic stem cells suppress the progression of human B-cell malignancies in xenograft animals.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- iPSC-Derived iNK Progenitors Engraft and Generate NK Cells in Unconditioned and Autologous Immune Humanized Mice.Cell proliferation · 2026Article
- CAR-NK cell therapy for hematologic malignancies: advances, challenges and optimization strategies.Molecular cancer · 2026Review
- Dual-module aCAR-iCAR NK cells for solid tumors: cascade resistance mechanisms, AI-driven engineering, and precision stratification.Frontiers in immunology · 2026Review
- Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease.Biology · 2025Review
- Engineered natural killer cells for cancer therapy.Cancer cell · 2025Review
- Targeting SHP-1-Mediated Inhibition of STAT3 and ERK Signalling Pathways Rescues the Hyporesponsiveness of MHC-I-Deficient NK-92MI.Cell proliferation · 2025Article
- Engineered CRO-CD7 CAR-NK cells derived from pluripotent stem cells avoid fratricide and efficiently suppress human T-cell malignancies.Journal of hematology & oncology · 2025Article
- Addressing graft-versus-host disease in allogeneic cell-based immunotherapy for cancer.Experimental hematology & oncology · 2025Review
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Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Chimeric antigen receptor (CAR) engineered natural killer (NK) cells exhibit advantages such as MHC-independent recognition and strong anti-tumor functions. However, allogeneic CAR-NK cells derived from human tissues are heterogeneous and susceptible to clearance by hosts. Methods: We generated a B2M knockout, HLA-E and CD19 CAR ectopic expressing embryonic stem cell (ESC) line, which differentiated normally and gave rise to homogeneous CD19 CAR-NK (CD19 CAR-UiNK) cells using an organoid aggregate induction method. The CD19 CAR-UiNK were co-cultured with T cells or NK cells derived from peripheral blood mononuclear cells (PBMC) with the mismatched HLA to evaluate the immunogenicity of CD19 CAR-UiNK cells. We further assessed the therapeutic effects of CD19 CAR-UiNK cells on CD19 Results: The CD19 CAR-UiNK cells exhibited typical expression patterns of activating and inhibitory receptors, and crucial effector molecules of NK cells, similar to those of unmodified NK cells. In co-culture assays, the CD19 CAR-UiNK cells evaded allogeneic T cell response and suppressed allogeneic NK cell response. Functionally, the CD19 CAR-UiNK cells robustly secreted IFN-γ and TNF-α, and upregulated CD107a upon stimulation with Nalm-6 tumor cells. The CD19 CAR-UiNK cells effectively eliminated CD19 Conclusion: We offer a strategy for deriving homogeneous and hypoimmunogenic CD19 CAR-iNK cells with robust anti-tumor effects from ESCs. Our study has significant implications for developing hypoimmunogenic CD19 CAR-NK cell therapy using human ESC as an unlimited cell source.
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