A study published in the journal ImmunoTherapy of Cancer highlights the importance of CAR T-cell affinity in targeting HER2 in solid tumors. The research team developed a murine model to evaluate the safety and efficacy of HER2-targeting CAR T cells. They found that high-affinity CAR T cells, while effective in recognizing HER2 on tumor cells, caused toxicity to normal HER2-positive tissues, independent of tumor burden. In contrast, low-affinity CAR T cells effectively targeted HER2-positive tumors without causing toxicity. The study emphasizes that for targets like HER2, which are expressed on normal tissues, low-affinity CARs are safer and more effective. The findings suggest that using low-affinity HER2 CAR T cells could be a promising approach for treating solid tumors with high HER2 expression. The study also highlights the need to consider factors such as CAR T-cell dose, lymphodepletion intensity, and CAR affinity when designing CAR T therapies for targets expressed on normal tissues. The research underscores the importance of preclinical models in understanding the balance between therapeutic efficacy and toxicity in CAR T therapy.A study published in the journal ImmunoTherapy of Cancer highlights the importance of CAR T-cell affinity in targeting HER2 in solid tumors. The research team developed a murine model to evaluate the safety and efficacy of HER2-targeting CAR T cells. They found that high-affinity CAR T cells, while effective in recognizing HER2 on tumor cells, caused toxicity to normal HER2-positive tissues, independent of tumor burden. In contrast, low-affinity CAR T cells effectively targeted HER2-positive tumors without causing toxicity. The study emphasizes that for targets like HER2, which are expressed on normal tissues, low-affinity CARs are safer and more effective. The findings suggest that using low-affinity HER2 CAR T cells could be a promising approach for treating solid tumors with high HER2 expression. The study also highlights the need to consider factors such as CAR T-cell dose, lymphodepletion intensity, and CAR affinity when designing CAR T therapies for targets expressed on normal tissues. The research underscores the importance of preclinical models in understanding the balance between therapeutic efficacy and toxicity in CAR T therapy.