Background: The Promise and Challenge of Immunotherapies
Years of research on the role of the immune system in targeting cancer cells has resulted in immunotherapeutic technologies such as CAR-T cell therapies and check-point inhibitors that are effective in combating various cancers. However, the success of these therapies has been tempered by challenges regarding the variable effectiveness across patients and tumor types.
Targeting the adaptive immune system’s T cells via CAR-T cell therapies has also been shown to cause significant adverse affects in some patients. However, therapies based on the innate immune system’s natural killer (NK) cells have a more favorable safety profile while exhibiting potent anti-tumor activity.
Despite the strong anti-tumor activity of NK cells, it is difficult for these cells to penetrate solid tumors, and monitoring their delivery to tumors is a challenge. To this end, scientists have investigated a means to improve cancer cell killing efficiency, NK-cell homing, and tracking of NK cells to solid tumors.
Novel Approach to Activating NK Cells
Scientists from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University have developed a nanoparticle-based approach to label and activate NK cells that have an enhanced capacity to kill cancer cells when injected into solid tumors of rat models of hepatocellular carcinoma.
The researchers designed magnetic nanocomplexes using hyaluronic acid, protamine, and ferumoxytol (a superparamagnetic iron oxide nanoparticle) to label NK cells. The nanocomplexes, referred to as HAPF, were well able to attach to NK cells. The labeled NK cells (HAPF-NK) were then activated with application of an exogenous magnetic field, causing the secretion of NK-cell lytic granules.
Design of the HAPF-NK cells allowed magnetic resonance imaging (MRI) to be used to guide direct injection of the hepatocellular tumors with the activated cells via intra-arterial infusion. The researchers took MRI scans at baseline and various points after injection up to over a week post-injection, then the pre- and post-injection tumor sizes were measured.
The study results showed a suppression of tumor growth after treatment with the activated HAPF-NK cells. There was a significant difference in the tumor volumes between control and NK cell infusion groups, as well as a significant difference in the tumor sizes between those observed at baseline and several days post-injection.
Magnetic activation of the NK cells enhanced homing and their capacity to kill cancer cells in solid tumors. The approach allowed the use of MRI imaging to guide and monitor NK cell delivery to tumors. This information can be harnessed to develop NK cell−based immunotherapies for a diversity of solid tumors and address a major challenge of immunotherapies today.
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