Abstract
Molecular imaging is a relatively new discipline that allows visualization, characterization, and measurement of the biological processes in living subjects, including humans, at a cellular and molecular level. The interaction between cancer cells and natural killer (NK) cells is complex and incompletely understood. Despite our limited knowledge, progress in the search for immune cell therapies against cancer could be significantly improved by dynamic and non-invasive visualization and tracking of immune cells and by visualization of the response of cancer cells to therapies in preclinical and clinical studies. Molecular imaging is an essential tool for these studies, and a multimodal molecular imaging approach can be applied to monitor immune cells in vivo, for instance, to visualize therapeutic effects. In this review, we discuss the usefulness of NK cells in cancer therapies and the preclinical and clinical usefulness of molecular imaging in NK cell-based therapies. Furthermore, we discuss different molecular imaging modalities for use with NK cell-based therapies, and their preclinical and clinical applications in animal and human subjects. Molecular imaging has contributed to the development of NK cell-based therapies against cancers in animal models and to the refinement of current cell-based cancer immunotherapies. Developing sensitive and reproducible non-invasive molecular imaging technologies for in vivo NK cell monitoring and for real-time assessment of therapeutic effects will accelerate the development of NK cell therapies.
Highlights
Over the past few decades, imaging has changed the way medicine is practiced
We have previously demonstrated the therapeutic effects of natural killer (NK) cells in vitro on doxorubicin-sensitive and -resistant breast cancer cells, with in vitro molecular imaging using bioluminescent reporter genes [94]
We showed the in vivo therapeutic efficiency of NK cells in breast cancer cells by means of in vivo molecular imaging using bioluminescent reporter genes [96]
Summary
Over the past few decades, imaging has changed the way medicine is practiced. Recent advances in molecular imaging allow the visualization of both cellular and subcellular biological and pathophysiological processes within living subjects [1]. NK-92 is currently the only NK cell line that has entered clinical trials and that can serve as a platform for studying NK cell-based tumor immunotherapy to date [14] This cell line proliferates and expands with a doubling time of 4 days, and the cells can be administered to patients repeatedly [34]. Overexpression of activating and inhibitory receptors might be effective in modulating and enhancing NK cell–tumor interactions This gene modification approach resulted in a stronger intracellular cytotoxic signal and increased tumor cell killing by NK cells [32, 44, 45]. Despite their successes, conventional histopathological and cytological methods have significant limitations when used in biological experiments. Molecular imaging allows monitoring of time-dependent experimental, developmental, environmental, and therapeutic effects of NK cell-based treatments in the same animal or patient
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