ArticleJournal for immunotherapy of cancer2021
Engineering CAR-NK cells to secrete IL-15 sustains their anti-AML functionality but is associated with systemic toxicities.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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
136 citing papers in PubMed, 150 citations in OpenAlex.
- Recent advances of cell therapies for AML/MDS: exploring the therapeutic potential of innate immune cells in AML/MDS.International journal of hematology · 2026Review
- CAR design equips diverse immune cells with unique antigen-specific activation identities.Molecular therapy. Oncology · 2026Article
- Natural killer cells against viral infection: from basic biology to immunotherapy.Precision clinical medicine · 2026Review
- Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.Cell reports. Medicine · 2026Review
- Multifunctional-engineered NK cells overcome tumor immunosuppression by combining PD-L1 and HLA-E targeting and endogenous IL15 production.Signal transduction and targeted therapy · 2026Article
- Circumventing Ewing sarcoma tumor microenvironment resistance by IL1RAP CAR-modified TGFβ1-imprinted natural killer cells in combination with IL-15 agonist and anti-GD2 antibody.Journal for immunotherapy of cancer · 2026Article
- Next-generation CAR-NK cell therapy: engineering strategies, translational challenges, and future perspectives in cancer immunotherapy.Cancer cell international · 2026Review
- Efficient, fratricide free non-viral engineering of CD70-targeted CAR NK cells for hematologic and solid tumor immunotherapy.Molecular therapy. Advances · 2026Article
- Exploring CAR cell therapies beyond CAR-T for myeloid malignancies.Journal of biomedical science · 2026Review
- In vivo CAR-M therapy: advancing precision delivery and programmable immune remodeling.Cell communication and signaling : CCS · 2026Review
- Review
- PTPN1/PTPN2 inhibition improves NK cancer therapy by enhancing IL-2 and mitigating TGFβ1 responses.EMBO reports · 2026Article
- Progress in cell-based immunotherapies for solid tumors.Discover oncology · 2026Review
- Constitutive RLI Armoring Enhances CAR-NK Cell Effector Functions but Causes Lethal Toxicity In Vivo.International journal of molecular sciences · 2026Article
- Article
- CAR-NK cell therapy for hematologic malignancies: advances, challenges and optimization strategies.Molecular cancer · 2026Review
- Non-viral TcBuster transposon engineering of CD70-CAR natural killer cells for the treatment of osteosarcoma.Molecular therapy. Oncology · 2026Article
- Co-Expression of IL-2 Enhances the Efficacy of FLT3-CAR-γδT Cells in Acute Myeloid Leukemia.Cancers · 2026Article
- A framework integrating multiscale in silico modeling and experimental data predicts CAR-NK cell cytotoxicity across target cell types.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Engineering with EP2/EP4 knockout and IL-15 transpresentation renders stem cell-derived NK cells self-persistent and resistant to PGE2 inhibition.Frontiers in immunology · 2026Article
76 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
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe prognosis of patients with recurrent/refractory acute myelogenous leukemia (AML) remains poor and cell-based immunotherapies hold promise to improve outcomes. Natural Killer (NK) cells can elicit an antileukemic response via a repertoire of activating receptors that bind AML surface ligands. NK-cell adoptive transfer is safe but thus far has shown limited anti-AML efficacy. Here, we aimed to overcome this limitation by engineering NK cells to express chimeric antigen receptors (CARs) to boost their anti-AML activity and interleukin (IL)-15 to enhance their persistence.
methodsWe characterized in detail NK-cell populations expressing a panel of AML (CD123)-specific CARs and/or IL-15 in vitro and in AML xenograft models.
resultsCARs with 2B4.ζ or 4-1BB.ζ signaling domains demonstrated greater cell surface expression and endowed NK cells with improved anti-AML activity in vitro. Initial in vivo testing revealed that only 2B4.ζ Chimeric Antigen Receptor (CAR)-NK cells had improved anti-AML activity in comparison to untransduced (UTD) and 4-1BB.ζ CAR-NK cells. However, the benefit was transient due to limited CAR-NK-cell persistence. Transgenic expression of secretory interleukin (sIL)-15 in 2B4.ζ CAR and UTD NK cells improved their effector function in the setting of chronic antigen simulation in vitro. Multiparameter flow analysis after chronic antigen exposure identified the expansion of unique NK-cell subsets. 2B4.ζ/sIL-15 CAR and sIL-15 NK cells maintained an overall activated NK-cell phenotype. This was confirmed by transcriptomic analysis, which revealed a highly proliferative and activated signature in these NK-cell groups. In vivo, 2B4.ζ/sIL-15 CAR-NK cells had potent anti-AML activity in one model, while 2B4.ζ/sIL-15 CAR and sIL-15 NK cells induced lethal toxicity in a second model.
conclusionTransgenic expression of CD123-CARs and sIL-15 enabled NK cells to function in the setting of chronic antigen exposure but was associated with systemic toxicities. Thus, our study provides the impetus to explore inducible and controllable expression systems to provide cytokine signals to AML-specific CAR-NK cells before embarking on early-phase clinical testing.
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.