ArticleJournal of experimental & clinical cancer research : CR2025
A chimeric antigen receptor tailored to integrate complementary activation signals potentiates the antitumor activity of NK cells.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed.
- A Novel Strategy to Produce CAR-γδ T Cells via Site-Directed Gene Integration by a Combination of CRISPR/Cas9 and AAV.Cancer medicine · 2026Article
- CAR-NK cell therapy for hematologic malignancies: advances, challenges and optimization strategies.Molecular cancer · 2026Review
- CLL-1: An emerging target for immunotherapy in acute myeloid leukemia.Annals of hematology · 2026Review
- Redefining cell therapy: CAR-engineered innate immune cells to conquer solid and hematologic malignancies.Molecular biology reports · 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
- Targeting the synovial engine: next-generation engineered immune cells to eradicate pathogenic FLS in rheumatoid arthritis, with safety-first, selective designs.Frontiers in immunology · 2026Review
- Dual-module aCAR-iCAR NK cells for solid tumors: cascade resistance mechanisms, AI-driven engineering, and precision stratification.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
- Natural Killer Cell Therapy in Ovarian Cancer: From Preclinical Potentials to Clinical Applications and Combination Strategies.International journal of biological sciences · 2026Review
- CAR-NK Engineering to Overcome TME Barriers.Cells · 2025Review
- Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease.Biology · 2025Review
- Review
- Application and prospects of genetic engineering in CAR-NK cell therapy.Frontiers in immunology · 2025Review
- Engineering the next generation of CAR T- cells: precision modifications, logic gates and universal strategies to overcome exhaustion and tumor resistance.Frontiers in oncology · 2025Review
- 2B4 co-stimulation and dasatinib modulation enhance anti-CD19 CAR-NK-92 cell cytotoxicity.Frontiers in immunology · 2025Article
- Does a natural killer need a CAR?Frontiers in immunology · 2025Review
- Engineering immunity with CAR-NK cells: advancing the frontiers of cancer immunotherapy.Frontiers in pharmacology · 2025Review
- CAR-γδ T cells: a new paradigm of programmable innate immune sentinels and their systemic applications in cancer and beyond.Frontiers in immunology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
backgroundChimeric antigen receptors (CARs) are synthetic receptors that reprogram the target specificity and functions of CAR-expressing effector cells. The design of CAR constructs typically includes an extracellular antigen-binding moiety, hinge (H), transmembrane (TM), and intracellular signaling domains. Conventional CAR constructs are primarily designed for T cells but have been directly adopted for other effector cells, including natural killer (NK) cells, without tailored optimization. Given the benefits of CAR-NK cells over CAR-T cells in terms of safety, off-the-shelf utility, and antigen escape, there is an increasing emphasis on tailoring them to NK cell activation mechanisms.
methodsWe first have taken a stepwise approach to modifying CAR components such as the combination and order of the H, TM, and signaling domains to achieve such tailoring in NK cells. Functionality of NK-tailored CARs were evaluated in vitro and in vivo in a model of CD19-expressing lymphoma, along with their expression and signaling properties in NK cells.
resultsWe found that NK-CAR driven by the synergistic combination of NK receptors NKG2D and 2B4 rather than DNAM-1 and 2B4 induces potent activation in NK cells. Further, more effective CAR-mediated cytotoxicity was observed following the sequential combination of DAP10, but not NKG2D TM, with 2B4 signaling domain despite the capacity of NKG2D TM to recruit endogenous DAP10 for signaling. Accordingly, an NK-CAR incorporating DAP10, 2B4, and CD3ζ signaling domains coupled to CD8α H and CD28 TM domains was identified as the most promising candidate to improve CAR-mediated cytotoxicity. This NK-tailored CAR provided more potent antitumor activity than a conventional T-CAR when delivered to NK cells both in vitro and in vivo.
conclusionsHence, NK receptor-based domains hold great promise for the future of NK-CAR design with potentially significant therapeutic benefits.
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.