AI Article Synopsis
- This study focuses on the development of HER2-targeted chimeric antigen receptor natural killer (CAR-NK) cells as a potential therapy for ovarian cancer, offering a less complex and more cost-effective alternative to traditional CAR T cell therapies.
- CAR-NK cells were genetically modified to express both a HER2-targeted CAR and a PET reporter gene, allowing for better tracking and imaging of these immune cells after administration.
- Experimental results demonstrated that CAR-NK cells were more effective in killing cancer cells, reducing tumor size and improving survival in mice, while also allowing for successful monitoring through bioluminescence and PET imaging techniques.
Article Abstract
Chimeric antigen receptor (CAR) cell therapies utilize CARs to redirect immune cells towards cancer cells expressing specific antigens like human epidermal growth factor receptor 2 (HER2). Despite their potential, CAR T cell therapies exhibit variable response rates and adverse effects in some patients. Non-invasive molecular imaging can aid in predicting patient outcomes by tracking infused cells post-administration. CAR-T cells are typically autologous, increasing manufacturing complexity and costs. An alternative approach involves developing CAR natural killer (CAR-NK) cells as an off-the-shelf allogeneic product. In this study, we engineered HER2-targeted CAR-NK cells co-expressing the positron emission tomography (PET) reporter gene human sodium-iodide symporter (NIS) and assessed their therapeutic efficacy and PET imaging capability in a HER2 ovarian cancer mouse model.NK-92 cells were genetically modified to express a HER2-targeted CAR, the bioluminescence imaging reporter Antares, and NIS. HER2-expressing ovarian cancer cells were engineered to express the bioluminescence reporter Firefly luciferase (Fluc). Co-culture experiments demonstrated significantly enhanced cytotoxicity of CAR-NK cells compared to naive NK cells. In vivo studies involving mice with Fluc-expressing tumors revealed that those treated with CAR-NK cells exhibited reduced tumor burden and prolonged survival compared to controls. Longitudinal bioluminescence imaging demonstrated stable signals from CAR-NK cells over time. PET imaging using the NIS-targeted tracer 18F-tetrafluoroborate ([F]TFB) showed significantly higher PET signals in mice treated with NIS-expressing CAR-NK cells.Overall, our study showcases the therapeutic potential of HER2-targeted CAR-NK cells in an aggressive ovarian cancer model and underscores the feasibility of using human-derived PET reporter gene imaging to monitor these cells non-invasively in patients.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368970 | PMC |
| http://dx.doi.org/10.1007/s00259-024-06722-w | DOI Listing |
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