What are the limitations of CAR-T cell therapy?

One limitation is that tumor cells have the ability to evade recognition by CAR-T cells by decreasing the expression of the target antigen. This process is known as antigen escape. Another limitation is on-target off-tumor effects, in which engineered T-cells  inadvertently recognize and attack healthy tissue. Another con is that tumors create a hostile microenvironment that suppresses immune responses through various mechanisms. CAR-T cells can also induce toxicity through various mechanisms. One potential  mechanism of toxicity is when CAR -T cells cross-react with proteins present on normal tissues that are not expressed on tumor cells. The most well-known and significant toxicity associated with CAR-T cells is cytokine release syndrome (CRS). This condition is characterized by symptoms such as fever and low blood pressure.