ArticleCancer immunology, immunotherapy : CII2023
Cytotoxicity of CD19-CAR-NK92 cells is primarily mediated via perforin/granzyme pathway.
Article in Cancer immunology, immunotherapy : CII, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- Anti-BCMA CAR-NK Cells Reveal Enhanced Cytolytic and Secretory Responses Against Myeloma Cells.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2026Article
- The microbiota-NK cell axis in colorectal cancer: a spatial and subset-centric framework.Frontiers in immunology · 2026Review
- Chimeric antigen receptor macrophages therapy for glioblastoma: challenges and opportunities from preclinical evidence to clinical translation.Frontiers in immunology · 2026Review
- Review
- Anti-Her2 CAR-NK92 Cells and Their Exosomes: Generation, Characterization, and Selective Cytotoxicity Against Her2-Positive Tumor Cells.International journal of molecular sciences · 2025Article
- Nanobody-Based CAR NK Cells for Possible Immunotherapy of MesothelinImmune network · 2025Article
- Sonodynamic Therapy Induces Pyroptosis and Recruits CAR-NK Cells to Enhance the Treatment of Oral Squamous Cell Carcinoma.ACS applied materials & interfaces · 2025Article
- Article
- Engineered NK92 cell-derived exosomes inhibit ovarian cancer progression by degradingFrontiers in immunology · 2025Article
- Highly sensitive live-cell imaging-based cytotoxicity assay enables functional validation of rare epitope-specific CTLs.Frontiers in immunology · 2025Article
- Perforin 1 in Cancer: Mechanisms, Therapy, and Outlook.Biomolecules · 2024Review
- The potential of organoids in renal cell carcinoma research.BMC urology · 2024Review
- Granzymes in health and diseases: the good, the bad and the ugly.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptors (CARs) have improved cancer immunotherapy in recent years. Immune cells, such as Natural killer cells (NK-cells) or T cells, are used as effector cells in CAR-therapy. NK92-cells, a cell line with known cytotoxic activity, are of particular interest in CAR-therapy since culturing conditions are simple and anti-tumor efficacy combined with a manageable safety profile was proven in clinical trials. The major pathways of immune effector cells, including NK92-cells, to mediate cytotoxicity, are the perforin/granzyme and the death-receptor pathway. Detailed knowledge of CAR-effector cells' cytotoxic mechanisms is essential to unravel resistance mechanisms, which potentially arise by resistance against apoptosis-inducing signaling. Since mutations in apoptosis pathways are frequent in lymphoma, the impact on CAR-mediated cytotoxicity is of clinical interest. In this study, knockout models of CD19-CAR-NK92 cells were designed, to investigate cytotoxic pathways in vitro. Knockout of perforin 1 (Prf1) and subsequent abrogation of the perforin/granzyme pathway dramatically reduced the cytotoxicity of CD19-CAR-NK92 cells. In contrast, knockout of FasL and inhibition of TRAIL (tumor necrosis factor-related apoptosis-inducing ligands) did not impair cytotoxicity in most conditions. In conclusion, these results indicate the perforin/granzyme pathway as the major pathway to mediate cytotoxicity in CD19-CAR-NK92 cells.
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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.