Reacción a "Reactions: two studies add circuitry to CAR-T cells to improve immunotherapy"

The studies have been conducted by two research groups with a long history in synthetic biology and immunotherapy, one led by Wendell A. Lim at the University of California San Francisco and the other led by Ahmad S. Khalil at Boston University. The papers are of excellent quality.  

Both papers present synthetic biology-based strategies to improve the efficacy and safety of cell-based cancer immunotherapies, in particular T lymphocytes directed via chimeric antigen receptors (CARs) to predefined tumour targets. Although initially focused on cancer, these approaches could have important future applications in other pathologies. In both cases, the aim is to overcome the physiological limits associated with "natural" immune responses and establish systems that can be regulated, by interactions with specific tumour targets or by drugs, to enhance, regulate or modulate the immune response. These studies will make it possible to extend the efficacy of CAR-T cells in solid tumours, hitherto not very sensitive to this type of therapy, and to improve the toxicity profile of these treatments. In addition, these studies will further develop a concept of great interest in this field, the so-called "dynamic adjustment", which aims to regulate the state of CAR-T cells (active vs. resting) to prevent "cell exhaustion" and enhance anti-tumour responses. 

The limitations are those set by tumours, such as clonal heterogeneity, barriers to access to immune infiltration, "brakes" on effector cell functions, etc. I have no doubt that these or similar systems will be the basis for future personalised immunotherapies, which will be equipped with "countermeasures" to counteract the limitations that each tumour may develop.