Abstract: Acute myeloid leukemia (AML) remains largely unresponsive to classical immunotherapeutic interventions other than allogeneic stem cell transplantation. Within this context, the major challenge remains the very low mutational load of AML when compared to other diseases, which makes AML initially appear to be less suitable for currently available immune therapies.
The concept of TEGs (abT cell engineered to express a defined gdTCR) provides a promising treatment option for many patients suffering from cancer with low mutational load such as AML, by targeting the RhoB-CD277 axis. Due to this project we aim a more precise molecular understanding of AML targeting by TEGs, which will allow for improved identification of patients who would benefit from this type of immune therapy. In addition while the first human clinical trials with this concept have been initiated, this project will help to understand how efficacy and toxicity of TEGs are balanced, as well as how mechanisms of tolerance active against these most optimized engineered immune cells can be overcome to improve overall efficacy.