| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Zhang, Pengchao Feng, Xuejia Niu, Xiangyun Liu, Zhongming Li, Minghui Liu, Maoxuan Yan, Dehong Zhang, Guizhong Wan, Xiaochun |
| 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. |
| Related Links | https://ehoonline.biomedcentral.com/counter/pdf/10.1186/s40164-025-00618-7.pdf |
| Ending Page | 5 |
| Page Count | 5 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 21623619 |
| DOI | 10.1186/s40164-025-00618-7 |
| Journal | Experimental Hematology & Oncology |
| Issue Number | 1 |
| Volume Number | 14 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2025-03-03 |
| Access Restriction | Open |
| Subject Keyword | Hematology Oncology Cancer Research CAR-NK Transcriptomics CD28 4-1BB MAP3K8 |
| Content Type | Text |
| Resource Type | Correspondence |
| Subject | Hematology Oncology Cancer Research |
| Journal Impact Factor | 9.4/2023 |
| 5-Year Journal Impact Factor | 8.3/2023 |
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