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

One of the biggest threats to womens lives and health is breast cancer, with HER2+ breast cancer accounting for a significant proportion of cases. This subtype is characterized by aggressive behavior, a high recurrence rate, and generally poor prognosis. While traditional HER2-CAR-T cell therapy has proven to show great success in treating HER2+ breast cancer, it carries the risk of on-target off-tumor toxicity, which could be life-threatening for patients. This review outlines the challenges associated with traditional HER2-CAR-T cell therapy and explores current strategies aimed at mitigating on-target off-tumor toxicity. The review categorizes these strategies into three main approaches, providing a comprehensive overview to help the medical and research community better understand the current state and future directions of HER2-CAR-T cell therapy. 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 cell therapies. A thorough understanding of the current challenges and promising avenues for enhancement in HER2-CAR-T cell therapy is essential for advancing future research and clinical applications.