Combined approaches to cancer therapy: from synthetic promoters in CAR therapy to artificial reporters for precision cancer medicine

Harnessing immune effector cells to benefit cancer patients is becoming more and more prevalent in recent years. However, the increasing number of different therapeutic approaches, such as chimeric antigen receptors (CAR) and armored chimeric antigen receptors, requires constant adjustments of the transgene expression levels. In particular, the danger of an overt life-threatening immune response due to the ON-target OFF-tumor CAR cytotoxicity should be considered. We developed synthetic promoters to induce the expression of the CAR immune-effectors within the tumor microenvironment (TME); we will discuss the effect of optimized promoter-responsive elements and minimal promoters on the function of the synthetic promoters in the TME. In addition to CAR-based therapy, immune checkpoint inhibitors (ICI)-based therapy is imperative today in immunotherapy of cancer. Accurate predictive biomarkers of response to ICIs are required for better stratifying cancer patients to ICI treatments. We developed a new concept for a bioassay to predict the response to ICIs that is based on measuring the binding functionality of immunomodulating ligands to their receptor(s) and we will discuss our findings regarding PD1-based ICI therapy.