An interdisciplinary research project conducted by Karl Landsteiner University of Health Sciences and the University for Continuing Education Krems is developing an innovative 3D co-culture system to improve NK cell immunotherapy for acute myeloid leukemia (AML).The aim is to prevent relapses and reduce animal testing with mimicking models.
Acute myeloid leukemia (AML) is a hematopoietic disease characterized by an overproduction of myeloid precursor and stem cells.
The incidence is approximately 3.7 cases per 100,000 inhabitants per year. Although new targeted therapies have been developed in recent years, the recurrence of the disease, known as relapse in technical terms, remains a major problem. Immunotherapy with natural killer cells, or NK cells for short, shows promise in counteracting relapses. "Since AML is a bone marrow cancer, it is particularly important to understand the interaction of NK cells with leukemic cells in this niche in order to improve the effectiveness of adoptive NK cell therapies. The main goal of this project is therefore to establish a 3D co-culture system that mimics the bone marrow niche in order to better evaluate NK cell immunotherapies for AML," says project leader Agnieszka Witalisz-Siepracka from the Karl Landsteiner University of Health Sciences.
This approach could serve as a precursor to in vivo experiments, thereby reducing the need for animal testing. According to Witalisz-Siepracka, this model will be the first to test the influence of mesenchymal stem cells, the key regulatory cell type in the bone marrow niche, on the escape of AML cells from NK cells in a complex 3D tumor microenvironment.
-UWK%20Walter%20Skokanitsch.jpg "© UWK Walter Skokanitsch")
An innovative 3D co-culture system aims to improve NK cell immunotherapy for acute myeloid leukaemia. The University of Continuing Education is contributing its expertise in stem cell and immunology research to the joint research project with Karl Landsteiner University of Health Sciences.
Advancing NK cell-based therapies
The added value of this research project, funded by GFF Lower Austria, lies in the development of new models for investigating the evasion mechanisms of AML against NK cells in the bone marrow niche. The aim is to advance the optimization of NK cell-based therapies. The established 3D model is planned as a platform that is compatible with high-throughput assays and will significantly enrich translational cancer research. Drugs and other immunomodulatory substances will be tested for their effect on increasing NK cell-mediated killing of AML cells.
Detailed transcriptome characterization at the single-cell level, supplemented by secretome analysis of the 3D triculture, is the second objective of this study. In the future, such an approach will enable research into novel strategies for improving the killing of AML cells by NK cells. In the long term, such an approach could serve as a personalized platform for testing the sensitivity of primary AML blasts to NK cells. The combination of the Karl Landsteiner University of Health Sciences' long-standing expertise in NK cell biology and acute myeloid leukemia with the University for Continuing Education Krems' expertise in 3D cultures provides a unique opportunity to pursue this interdisciplinary project.
“The University for Continuing Education Krems specializes in stem cell and immunology research, with a particular focus on the development of advanced cellular models,” explains Sabrina Summer, who leads the team at the University of Krems. “Our team recently established a de novo angiogenesis model and is currently developing 3D culture systems for mesenchymal stem cells (MSCs) in various environments, including cartilage and bone marrow. In addition, we have extensive expertise in researching the immunoregulatory functions of MSCs under physiological and pathological conditions.”
Start with the establishment of a 3D matrix
The project, which began in July 2025, is designed to run for three years and comprises four project phases. Step one is the establishment of a 3D matrix for investigating NK cell-mediated surveillance of AML. Work on this is well advanced. The gel composition for the 3D co-culture of AML cells, MSCs, and NK cells has been optimized, and cytotoxicity assays based on confocal microscopy have been performed. A 3D matrix platform is also currently being improved to enable cell-based assays with living cells after 3D cultivation in alginate gels.
The project utilizes a wide range of equipment from the Core Facility Campus Krems for its research work. The Cytoflex flow cytometer, the Cytoflex SRT cell sorter, the TCS SP8 confocal laser scanning microscope, the IXplore SPIN ScanR NoviSight microscope, and other equipment such as Chemidoc and TimsTof flex, a recent acquisition, are used.
Project overview:
Title: Mimicking the bone marrow niche – 3D culture as a new tool to
improve NK cell-based immunotherapies for AML
Duration: July 2025 to June 2028
Funding body: Society for Research Promotion Lower Austria m.b.H. as part of
the FIT Strategy Lower Austria 2021-2027
Partners: Karl Landsteiner University of Health Sciences
(Lead Agnieszka Witalisz-Siepracka PhD)
University for Continuing Education Krems
(Sabrina Summer PhD)
Tags
