A groundbreaking study led by Professor Sebyung Kang and Professor Sung Ho Park in the Department of Biological Sciences at UNIST has revealed a remarkable breakthrough in cancer treatment. The research team has successfully developed unprecedented „NK cell-engaging nanodrones“ that can selectively attack and eliminate cancer cells, offering a potential solution for stubborn cancer types.
The innate lymphoid cells, known as natural killer (NK) cells, play a crucial role in the body’s immune response to cancer. Numerous efforts have been made to harness the power of NK cells for the development of effective cancer therapies. Now, the research team has designed and fabricated extraordinary nanodrones that bind to NK cells, called NKeNDs, using AaLS protein cage nanoparticles.
These groundbreaking NKeNDs present cancer-targeting ligands such as HER2Afb or EGFRAfb and NK cell-recruiting ligands aCD16Nb simultaneously on the surface of the AaLS using the SpyCatcher/SpyTag protein ligation system. The dual-ligand-presenting NKeNDs, named HER2 @NKeND and EGFR@NKeND, have demonstrated the ability to selectively bind to HER2-overexpressing SK-OV-3 cells and EGFR-overexpressing MDA-MB-468 cells, as well as human NK cells.
The physical contact mediated by the NKeNDs between human NK cells and the target cancer cells activates the NK cells, enabling them to effectively eliminate the target cancer cells in vitro. Remarkably, administration of HER2 @NKeNDs together with human PBMCs in SK-OV-3 tumor-bearing mice facilitates the infiltration of activated human NK cells into the tumor sites. This significantly suppresses tumor growth without causing noticeable side effects.
This groundbreaking study demonstrates a novel approach to developing cancer-specific NK cell engagers using protein cage nanoparticles and recombinant cancer binders. It holds enormous potential for the selective treatment of previously stubborn cancer types.
Professor Kang Se-byung expressed his enthusiasm about the study, stating, „This research presents new possibilities for immunotherapy through nanodrones for delivering NK cells, addressing challenges such as the movement and survival of NK cells. Our goal is to create new opportunities for customized treatments selectively targeting different cancer types through further research, including cancer-specific immune cell induction.“
The study, published in the prestigious journal Nano Today on December 2, was conducted with generous support from the National Research Foundation of Korea (NRF), the Ministry of Science and ICT (MSIT), the University Key Research Institute (C5: Center for Cell to Cell Communication in the Cancer), and the SRC Cellular Responses to Metabolic Stress Research Center (CRMSRC).
Ulsan National Institute of Science and Technology (UNIST)
Park, SG, et al. (2024). Protein cage nanoparticle-based NK cell-engaging nanodrones (NKeNDs) effectively recruit NK cells to attack tumor sites and suppress tumor growth. Nano Today. doi.org/10.1016/j.nantod.2023.102075.