Maria Mierzejewska

  Faculty of Science and Engineering| Maastricht Science Programme

Engineering CAR Macrophages (CAR-Ms) from Human Expanded Potential Stem Cells against Hepatic Cancer

Maria's elevator pitch
In recent years, iPSC-derived CAR macrophages (CAR-Ms) have emerged as a promising strategy for treating solid tumors due to their enhanced tumor infiltration capabilities. However, their clinical translation remains limited by low CAR expression during macrophage maturation and reduced antitumor activity compared to blood-derived CAR-Ms. This thesis addressed these challenges through a dual engineering strategy, aiming to achieve sustained CAR surface expression in mature macrophages. Firstly, CAR expression was driven under the macrophage-native STAT1 promoter to prevent transgene silencing. Secondly, a naturally occurring STAT1 gain-of-function mutation was leveraged to enhance macrophage inflammatory programming. Human EPSCs were differentiated into functional macrophages, and engineered cell lines were established, enabling a high-efficacy, scalable platform for CAR-M generation.