HER2-targeted CAR-NK cells and human-derived PET reporter gene imaging for ovarian cancer

Shalaby N, Xia Y, Kelly JJ, et al. Imaging CAR-NK Cells Targeted to HER2 Ovarian Cancer With Human Sodium-Iodide-Symporter-Based Positron Emission Tomography. European Journal of Nuclear Medicine and Molecular Imaging. 2024; (doi: 10.1007/s00259-024-06722-w).

New research supports the use of human-derived positron emission tomography (PET) reporter gene imaging after chimeric antigen receptor (CAR) infusion, as a tool to monitor immune cells deployed by the therapy and how well they are working. The non-invasive method is capable of predicting treatment outcomes in recipients, some of whom generate poor response rates and/or experience adverse effects. To evaluate PET imaging in the setting of human epidermal growth factor 2 (HER2)-positive ovarian cancer, scientists created an off-the-shelf allogeneic product. They started with natural killer (NK)-92 cells, well suited for this purpose because of their CAR-independent ability to eradicate cancer cells and their inhibition of graft-versus-host disease. The NK cells were modified to express a HER-directed CAR; human sodium-iodide symporter (NIS), a PET reporter gene; and the bioluminescence imaging reporter Antares. The resulting CAR-NK cells exhibited greater cytotoxicity versus naive NK cells in co-culture experiments. In vivo, mice with ovarian tumors engineered to express the bioluminescence reporter Firefly luciferase registered reduced tumor burden and longer survival when treated with CAR-NK cells.
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