Abstract
After the approval of five CAR-T therapies for the treatment of haematological malignancies, the next challenge in the field is generating novel CARs for the treatment of solid tumours. A main limitation is that certain combinations of CAR modules can result in chronic T cell activation in the absence of ligand (known as tonic signaling). Tonic signaling can induce T cell apoptosis, accelerated differentiation and impaired anti-tumor efficacy. Here, we hypothesized that the deleterious effects of tonic signaling can be reduced by optimizing CAR-T cell manufacturing conditions.
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