A pioneering study led by Prof. Sebyung Kang and Prof. Sung Ho Park in UNIST’s Department of Biological Sciences has revealed a remarkable breakthrough in cancer treatment. The research team successfully developed unprecedented “NK cell-engaging nanodrones” capable of selectively targeting and eliminating cancer cells, offering a potential solution for intractable types of cancer.
Innate lymphoid cells known as natural killer (NK) cells play a vital role in the body’s immune response against cancer. Numerous efforts have been made to harness the power of NK cells to develop effective cancer therapies. Now, the research team has designed and fabricated excellent NK cell-engaging nanodrones, referred to as NKeNDs, using AaLS protein cage nanoparticles.
These novel NKeNDs simultaneously display cancer targeting ligands, such as HER2Afb or EGFRAfb, and NK cell recruitment ligands, aCD16Nb, on the surface of AaLS via the SpyCatcher/SpyTag protein ligation system. NKeNDs displaying a double linker, named HER2@NKeND and EGFR@NKeND, have demonstrated the ability to selectively bind to HER2-overexpressing SK-OV-3 and EGFR-overexpressing MDA-MB-468 cells, respectively, as well as human cells NK cells.
Physical engagement of human NK cells with target tumor cells mediated by NKeNDs activates NK cells, allowing them to effectively eliminate target tumor cells in vitro. Remarkably, in SK-OV-3 tumor-bearing mice, administration of HER2 @NKeNDs together with human PBMCs facilitates infiltration of activated human NK cells into tumor sites. As a result, tumor growth is significantly suppressed without causing noticeable side effects.
This pioneering study presents a novel approach to develop cancer-specific NK cell targets using protein cage nanoparticles and recombinant tumor cell binders. It offers enormous potential for the selective treatment of previously untreatable types of cancer.
Professor Kang Se-byung expressed his excitement about the study, stating, “This research presents new possibilities for immunotherapy via nanodrones to deliver NK cells, overcoming challenges such as NK cell movement and survival. Our goal is to provide new opportunities for tailored therapies that selectively target various cancer types through further research, including cancer-specific immune cell challenge.”
The study, published in the journal Nano Today on December 2, was carried out with the generous support of the National Research Foundation of Korea (NRF), the Ministry of Science and ICT (MSIT), the University Basic Research Institute (C5: Center for Cell-Cell Communication in Cancer), and the SRC Cellular Responses to Metabolic Stress Research Center (CRMSRC).