ArticleExperimental hematology & oncology2025
CD28 is superior to 4-1BB costimulation in generating CAR-NK cells for tumor immunotherapy.
Article in Experimental hematology & oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
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Who cites it
11 citing papers in PubMed.
- Next-generation natural killer cell therapy: bench to bedside and beyond.Signal transduction and targeted therapy · 2026Review
- IL-15 boosts mesothelin- and CD70-CAR NK cell potency in PDAC without added benefit from dual targeting.Molecular therapy. Oncology · 2026Article
- Reprogramming Antitumor Immunity: NK Cell Strategies to Navigate the Immunosuppressive Tumor Microenvironment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CAR-NK cell therapy for hematologic malignancies: advances, challenges and optimization strategies.Molecular cancer · 2026Review
- Next-generation CAR-T and CAR-NK cell therapies in hematologic malignancies: engineering for persistence, specificity, and safety.Discover oncology · 2026Review
- Decoding signaling architectures: CAR versus TCR dynamics in solid tumor immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Enhancing CAR-NK persistence to unlock its full therapeutic potentials.Frontiers in immunology · 2026Review
- Generation of the augmented IL-15-secreting anti-HER2 chimeric antigen receptor (CAR)-NK cells: an encouraging immunotherapeutic tool.Molecular biology reports · 2025Article
- CRISPR/Cas9 TCR-Edited NKp30 CAR T Cells Exhibit Superior Anti-Tumor Immunity to B7H6-Expressing Leukemia and Melanoma.International journal of molecular sciences · 2025Article
- The role of immune checkpoint molecules in cancers.Frontiers in immunology · 2025Review
- Application and prospects of genetic engineering in CAR-NK cell therapy.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Chimeric antigen receptor (CAR)-NK therapy holds great potential for tumor treatment, but current CAR designs are primarily optimized for T cells, raising concerns about their suitability for NK cells. This study compared two dominant CAR designs used in T cells-CD28-CD3ζ (28z) and 4-1BB-CD3ζ (BBz)-and found that CD28 costimulation offers superior functionality in NK cells. 28z CAR-NK cells exhibited significantly better activation, cytotoxicity, and in vivo anti-tumor efficacy than BBz CAR-NK cells, with similar persistence and tumor infiltration. 28z CAR more effectively recruited the ZAP70 kinase and upregulated multiple key factors involved in immune activation, potentially augmenting CAR-NK cell function. MAP3K8, a kinase involved in inflammation and the MAPK signaling pathway, was identified as a critical mediator in enhancing 28z CAR-NK cell function. Silencing or inhibiting MAP3K8 impaired the anti-tumor activity of 28z CAR-NK cells, while its overexpression substantially improved the function of BBz CAR-NK cells. These findings provide new insights into how CD28 costimulation boosts CAR-NK cell efficacy, supporting its use into NK cell-specific CARs for cancer immunotherapy, and highlight MAP3K8 as a potential target for optimizing BBz CAR-NK cell therapy.
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