Adoptive cellular immunotherapy (ACT) based on T-cell receptors (TCR) or chimeric antigen receptors (CAR)-engineered T cells has emerged as a powerful approach to successfully combat aggressive and chemo-refractory acute leukemia. Natural killer (NK) cells represent another promising effector cell population for genetic modification with tumor-associated/specific antigens (TAA/TSA) specific CARs, thereby complementing endogenous innate natural cytotoxicity with the ability of targeted cell killing. However, the therapeutic efficacy in solid cancer is often hampered by multiple mechanisms such as down-regulation of tumor antigen expression, ineffective trafficking and homing of effector cells, dysregulated expression of checkpoint molecules (PD1, CTLA-4…), myeloid derived suppressor cells and/or regulatory T cells that can counteract T/NK cell effector functions.
Based on our longstanding expertise in the generation and improvement of TCRs against TAA/TSA and preclinical mouse model of anti-tumor adoptive cell therapy, our main research interests is to improve conventional T/NK cell-based tumor immunotherapy by (1) generating ‘off the shelf’ high-affinity tumor-reactive TCR/CARs with enhanced tumor recognition as well as reduced potential for unwanted off-target autoimmunity and (2) targeted inhibition of tumor-specific immune escape mechanisms. This combined approach has the potential to synergistically enhance the efficacy of anti-tumor immunotherapy as a prerequisite for its successful translational implementation in clinical practice as powerful targeted anti-cancer treatment.
Our group works in close collaboration with the Munder laboratory joining our respective scientific expertise. We are part of the German Consortium for Translational Cancer Research (DKTK) Frankfurt/Mainz (http://www.dktk.dkfz.de/de/home/) and involved in several multi-center translational immunotherapy/oncology programs.