Article: Empowering pancreatic tumor homing with augmented anti-tumor potency of CXCR2-tethered CAR-NK cells.
Molecular therapy. Oncology
2024 Volume 32, Issue 1, Page(s) 200777
Abstract: Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells are a promising immunotherapy for solid cancers; however, their effectiveness against pancreatic cancer is limited by the immunosuppressive tumor microenvironment. In particular, low NK ...
| Abstract | Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells are a promising immunotherapy for solid cancers; however, their effectiveness against pancreatic cancer is limited by the immunosuppressive tumor microenvironment. In particular, low NK cell infiltration poses a major obstacle that reduces cytotoxicity. The current study aimed to enhance the tumor-homing capacity of CAR-NK cells by targeting the chemokine-chemokine receptor axis between NK and pancreatic cancer cells. To this end, data from a chemokine array and The Cancer Genome Atlas pan-cancer cohort were analyzed. Pancreatic cancer cells were found to secrete high levels of ligands for C-X-C motif receptor 1 (CXCR1) and CXCR2. Subsequently, we generated anti-mesothelin CAR-NK cells incorporating CXCR1 or CXCR2 and evaluated their tumor-killing abilities in 2D cancer cell co-culture and 3D tumor-mimetic organoid models. CAR-NK cells engineered with CXCR2 demonstrated enhanced tumor killing and strong infiltration of tumor sites. Collectively, these findings highlight the potential of CXCR2-augmented CAR-NK cells as a clinically relevant modality for effective pancreatic cancer treatment. By improving their infiltration and tumor-killing capabilities, these CXCR2-augmented CAR-NK cells have the potential to overcome the challenges posed by the immunosuppressive tumor microenvironment, providing improved therapeutic outcomes. |
|---|---|
| Language | English |
| Publishing date | 2024-02-19 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 2950-3299 |
| ISSN | 2950-3299 |
| DOI | 10.1016/j.omton.2024.200777 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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