ArticleNature biotechnology2025
In vivo AAV-SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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Who cites it
36 citing papers in PubMed.
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Discovery and design of potent cell surface display elements.Nature biotechnology · 2026Article
- Next-generation CAR-NK cell therapy: engineering strategies, translational challenges, and future perspectives in cancer immunotherapy.Cancer cell international · 2026Review
- Balancing off-target and on-target considerations for optimized CRISPR-Cas9 knockout library design.Cell genomics · 2026Article
- Engineering NK and T cells with metabolite-sensing receptors to target solid tumors.Nature immunology · 2026Article
- Novel NK cell-like phenotype expressing CCR5 and its ligands elicits tumor-specific acquired immunity to carcinomatous peritonitis via host NK-derived IFN-γ.Journal for immunotherapy of cancer · 2026Article
- Genome-wide CRISPR screens in primary human natural killer cells identify countermeasures against immunosuppressive environment.Nature communications · 2026Article
- Article
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Engineering Immune Cell to Counteract Aging and Aging-Associated Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Genome-Wide CRISPR Screen Reveals PIK3CA Inhibition Enhances Lipid Nanoparticle-Mediated siRNA Delivery.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- A new era of natural killer cell immunotherapy in tumor treatment: latest advances and cutting-edge perspectives from basic research to clinical practice.Frontiers in immunology · 2026Review
- Ammonia metabolic reprogramming in the tumor microenvironment: emergence of an immunosuppressive niche.Frontiers in cell and developmental biology · 2026Review
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
- Harnessing the immune system: future directions in cancer immunotherapy.Frontiers in immunology · 2026Review
- Multidimensional plasticity of natural killer cells in tumours.Cell death & disease · 2025Review
- Convergence of mRNA technology and chimeric antigen receptor therapy: targeted technology optimizing targeted therapy.Journal of translational medicine · 2025Review
- Applications of Genome-wide Screening of CRISPR/Cas9 Knockout Library in Identifying Novel Molecular Targets for Xenobiotics.Environment & health (Washington, D.C.) · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Natural killer (NK) cells have clinical potential against cancer; however, multiple limitations hinder the success of NK cell therapy. Here, we performed unbiased functional mapping of tumor-infiltrating NK (TINK) cells using in vivo adeno-associated virus (AAV)-SB (Sleeping Beauty)-CRISPR (clustered regularly interspaced short palindromic repeats) screens in four solid tumor mouse models. In parallel, we characterized single-cell transcriptomic landscapes of TINK cells, which identified previously unexplored subpopulations of NK cells and differentially expressed TINK genes. As a convergent hit, CALHM2-knockout (KO) NK cells showed enhanced cytotoxicity and tumor infiltration in mouse primary NK cells and human chimeric antigen receptor (CAR)-NK cells. CALHM2 mRNA reversed the CALHM2-KO phenotype. CALHM2 KO in human primary NK cells enhanced their cytotoxicity, degranulation and cytokine production. Transcriptomics profiling revealed CALHM2-KO-altered genes and pathways in both baseline and stimulated conditions. In a solid tumor model resistant to unmodified CAR-NK cells, CALHM2-KO CAR-NK cells showed potent in vivo antitumor efficacy. These data identify endogenous genetic checkpoints that naturally limit NK cell function and demonstrate the use of CALHM2 KO for engineering enhanced NK cell-based immunotherapies.
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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.