Adoptive cellular immunotherapy (ACT) based on T-cell receptor (TCR) or chimeric antigen receptor (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 CARs specific for tumor-associated or tumor-specific antigens (TAA/TSA), 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 interests are 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 undesired 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 into 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 (https://dktk.dkfz.de/en/home) and involved in several multi-center translational immunotherapy/oncology programs.