On-target off-tumor (OTOT) toxicity from HER2-targeting chimeric antigen receptor (CAR) engineered T cell therapy: current solutions

Breast cancer is a major threat to women's life and health, with HER2+ BC accounting for a significant proportion of cases. This subtype is characterized by aggressive behavior, a high recurrence rate, and generally poor prognosis. The efficacy of conventional HER2-CAR-T treatment for HER2-positive breast cancer is well-documented; however, it is not without its risks, particularly the potential for on-target off-tumor (OTOT) toxicity, which poses a significant threat to patient safety. This analysis examines the difficulties encountered with standard HER2-CAR-T approaches and discusses contemporary methods designed to reduce the incidence of OTOT toxicity. This review organizes the strategies into three primary methods, offering an exhaustive summary to facilitate the medical and research sectors in gaining a deeper comprehension of the present scenario and prospective advancements of HER2-CAR-T treatment. By discussing these approaches and the underlying mechanisms that make them effective, this review aims to inspire further innovation in improving existing HER2-CAR-T therapy. A thorough understanding of the current challenges and promising avenues for enhancement in HER2-CAR-T therapy is quite important for advancing future research and clinical applications.