ArticleProceedings of the National Academy of Sciences of the United States of America2022
Memory-like NK cells armed with a neoepitope-specific CAR exhibit potent activity against NPM1 mutated acute myeloid leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Potential therapeutic roles of natural killer cells in acute myeloid leukemia: a systematic review study.Clinical and experimental medicine · 2025Pooled it
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 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
- Stem cell-based tactics in the remodeling and treatment of intestinal diseases.Stem cell research & therapy · 2026Review
- Non-viral targeted integration at the CISH locus enables CAR-NK cell engineering with enhanced anti-tumor activity.Molecular therapy. Oncology · 2026Article
- Exploring CAR cell therapies beyond CAR-T for myeloid malignancies.Journal of biomedical science · 2026Review
- Vascular STING activation facilitates NK cell anti-tumor immunity in small cell lung cancer.Cancer cell · 2026Article
- CAR-NK cell therapy for hematologic malignancies: advances, challenges and optimization strategies.Molecular cancer · 2026Review
- Macrophages From Latently Infected Mice Have Trained Immunity to HSV-1.Investigative ophthalmology & visual science · 2026Article
- Beyond αβ T cells: unlocking the potential of diverse immune cells in CAR modification.Clinical science (London, England : 1979) · 2026Review
- Defining the role of natural killer cells in acute myeloid leukemia through the lens of single-cell omics.Frontiers in immunology · 2026Review
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
- Harnessing the Power of CAR-NK Cells for Solid Tumors: Challenges, Innovations, and Future Frontiers in Immunotherapy.Cancer communications (London, England) · 2026Review
- Multidimensional plasticity of natural killer cells in tumours.Cell death & disease · 2025Review
- Multivalent aptamer engineered and functionalized NK cells for enhanced adoptive immunotherapy in CD30-positive malignant lymphoma.Molecular therapy. Nucleic acids · 2025Article
- CAR-NK cell therapy in multiple myeloma: from preclinical and clinical landscape to joining the force for treatment strategies optimization.Cell communication and signaling : CCS · 2025Review
- Selective HLA knockdown and PD-L1 expression prevent allogeneic CAR-NK cell rejection and enhance safety and anti-tumor responses in xenograft mice.Nature communications · 2025Article
- Review
- Engineering adoptive cell therapy for solid tumors.Medical oncology (Northwood, London, England) · 2025Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Acute myeloid leukemia (AML) remains a therapeutic challenge, and a paucity of tumor-specific targets has significantly hampered the development of effective immune-based therapies. Recent paradigm-changing studies have shown that natural killer (NK) cells exhibit innate memory upon brief activation with IL-12 and IL-18, leading to cytokine-induced memory-like (CIML) NK cell differentiation. CIML NK cells have enhanced antitumor activity and have shown promising results in early phase clinical trials in patients with relapsed/refractory AML. Here, we show that arming CIML NK cells with a neoepitope-specific chimeric antigen receptor (CAR) significantly enhances their antitumor responses to nucleophosphmin-1 (NPM1)-mutated AML while avoiding off-target toxicity. CIML NK cells differentiated from peripheral blood NK cells were efficiently transduced to express a TCR-like CAR that specifically recognizes a neoepitope derived from the cytosolic oncogenic NPM1-mutated protein presented by HLA-A2. These CAR CIML NK cells displayed enhanced activity against NPM1-mutated AML cell lines and patient-derived leukemic blast cells. CAR CIML NK cells persisted in vivo and significantly improved AML outcomes in xenograft models. Single-cell RNA sequencing and mass cytometry analyses identified up-regulation of cell proliferation, protein folding, immune responses, and major metabolic pathways in CAR-transduced CIML NK cells, resulting in tumor-specific, CAR-dependent activation and function in response to AML target cells. Thus, efficient arming of CIML NK cells with an NPM1-mutation-specific TCR-like CAR substantially improves their innate antitumor responses against an otherwise intracellular mutant protein. These preclinical findings justify evaluating this approach in clinical trials in HLA-A2
Indexed as
Identifiers
What OpenQuestion holds
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.