The doctoral dissertation in the field of Technical Physics will be examined at the Faculty of Science, Forestry and Technology, Kuopio campus.
What is the topic of your doctoral research? Why is it important to study the topic?
This doctoral research examines how immune-signaling molecules (cytokines), nanoparticle design, and nature-inspired (biomimetic) surface modifications surface modifications can be combined to shape innate immune responses, with a particular focus on natural killer (NK) cell activation. The aim was to investigate strategies to enhance NK cell-mediated antitumor immunity for cancer immunotherapy.
Cancer remains one of the leading causes of death worldwide. Immunotherapies have revolutionized cancer treatment, but many therapies still face challenges, including limited efficacy against solid tumors, patient and tumor heterogeneity and insufficient immune activation. Nanotechnology could provide solutions for more targeted and controlled activation of the immune system, thereby enhancing the body’s own immune response against cancer.
What are the key findings or observations of your doctoral research?
The work consisted of three parts. The first study investigated how different cytokine combinations and activation protocols affect NK cell expansion and function. The results showed that the activation protocol significantly affected NK cell proliferation, surface receptor expression, and their ability to kill cancer cells.
The second study focused on virus-like nanoparticles and demonstrated that their spike-like morphology enhances cellular uptake and modulates immune activation. In the final study, virus-like nanoparticles were modified with the cytokine IL-15 and cancer cell membranes, and their ability to induce immune activation was studied in mixed population of human peripheral blood immune cells (PBMC). Within PBMCs, NK cell activation was mainly mediated by monocytes, a type of immune cell that helps coordinate immune responses.
In this context, NK cell activation by virus-like nanoparticles depended on a combination of cytokine signaling, nanoparticle morphology, and interactions between different immune cells or activating surface molecules.
How can the results of your doctoral research be utilised in practice?
The results of this research can contribute to the development of new cancer immunotherapies. The biomimetic virus-like nanoparticles developed in this research provide a platform that could be used to support immune-cell activation and further develop strategies for NK-cell activation. In the future, these findings could support the development of more effective innate immune engaging cancer therapies as well as feeder-free NK cell expansion systems for advanced cell therapies.
What are the key research methods and materials used in your doctoral research?
The research utilised immune cells isolated from human peripheral blood, cancer cell models, flow cytometry, proteomics, microscopy, and methods for nanoparticle synthesis and characterisation. The physicochemical properties of the virus-like nanoparticles, including their spike morphology, surface charge, and composition, were characterised using methods such as dynamic light scattering (DLS) and transmission electron microscopy (TEM). NK cell activation and functionality were assessed based on surface receptor expression, cytokine secretion, and their ability to target and kill cancer cells.
The first study of my doctoral research was conducted at the Kuopio Center for Gene and Cell Therapy, currently Ferring Ventures Oy, while the final two studies were conducted in the Pharmaceutical Physics research group at the Department of Technical Physics, University of Eastern Finland. The research combines expertise from the fields of immunology, cancer immunotherapy, and nanotechnology.
The doctoral dissertation of Minna Sivonen, MSc, entitled Modulating immune cells with cytokines and biomimetic virus-like nanoparticles to enhance NK cell responses for cancer immunotherapy will be examined at the Faculty of Science, Forestry and Technology, Kuopio campus. The opponent will be Professor Benjamin Willcox, University of Birmingham, United Kingdom, and the custos will be Adjunct Professor Wujun Xu, University of Eastern Finland. Language of the public defence is English.
For further information, please contact:
Minna Sivonen, [email protected]
