ArticleScience advances2023
Loss of metabolic fitness drives tumor resistance after CAR-NK cell therapy and can be overcome by cytokine engineering.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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Who cites it
84 citing papers in PubMed, 96 citations in OpenAlex.
- DRP1 depletion protects NK cells from hypoxia-induced dysfunction.Redox report : communications in free radical research · 2026Article
- Advancing In Vivo Chimeric Antigen Receptor T-Cell Engineering to Accelerate Clinical Translation.MedComm · 2026Review
- PTPN22 as a novel therapeutic target: a key intracellular checkpoint for NK cell therapy.Journal for immunotherapy of cancer · 2026Article
- Siglec-7 orchestrates mitochondrial dynamics and metabolic reprogramming to restrain human NK cell cytotoxic function.The Journal of biological chemistry · 2026Article
- Nicotinamide mononucleotide potentiates the anti-tumor efficacy of CAR-NK cell therapy targeting MSLN in ovarian cancer.Cancer gene therapy · 2026Article
- Emerging Immune-Based Therapeutic Strategies in Hepatocellular Carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- CAR-NK cell therapy for hematological malignancies.Blood advances · 2026Review
- Article
- Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Engineered Mesenchymal Stem Cell-NK Cell Complexes for Spatially Targeted and Functionally Revitalized Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- CAR-engineering of innate and innate-like immune cells: a new horizon in adoptive cell therapy for solid tumors.Journal for immunotherapy of cancer · 2026Review
- Functional segregation of HIF-1α and AhR controls NK cell responsiveness under hypoxia.iScience · 2026Article
- Constitutive RLI Armoring Enhances CAR-NK Cell Effector Functions but Causes Lethal Toxicity In Vivo.International journal of molecular sciences · 2026Article
- Rapid CAR screening and circRNA-driven CAR-NK cells for persistent shed-resistant immunotherapy.Signal transduction and targeted therapy · 2026Article
- CAR-NK cell therapy for hematologic malignancies: advances, challenges and optimization strategies.Molecular cancer · 2026Review
- Engineering CLL-1 CAR-NK cells via mRNA-LNP for potent antitumor activity and reversal of HLA-E-mediated resistance in acute myeloid leukemia.Journal of experimental & clinical cancer research : CR · 2026Article
- Transcriptional networks weaving natural killer anti-tumor immune response.Molecular cancer · 2026Review
- Agent-based modeling of cellular dynamics in adoptive cell therapy.Communications biology · 2026Article
- Review
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
30 authors at 5 institutions in 2 countries.
Funding
Abstract
Chimeric antigen receptor (CAR) engineering of natural killer (NK) cells is promising, with early-phase clinical studies showing encouraging responses. However, the transcriptional signatures that control the fate of CAR-NK cells after infusion and factors that influence tumor control remain poorly understood. We performed single-cell RNA sequencing and mass cytometry to study the heterogeneity of CAR-NK cells and their in vivo evolution after adoptive transfer, from the phase of tumor control to relapse. Using a preclinical model of noncurative lymphoma and samples from a responder and a nonresponder patient treated with CAR19/IL-15 NK cells, we observed the emergence of NK cell clusters with distinct patterns of activation, function, and metabolic signature associated with different phases of in vivo evolution and tumor control. Interaction with the highly metabolically active tumor resulted in loss of metabolic fitness in NK cells that could be partly overcome by incorporation of IL-15 in the CAR construct.
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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.