Warming-up the immune cell engagers (ICEs) era in breast cancer: state of the art and future directions

The advent of immune checkpoint inhibitors (ICIs) has deeply reshaped the therapeutic algorithm of triple-negative breast cancer (TNBC). However, there is considerable scope for better engagement of the immune system in other BC subtypes. ICIs have paved the way for investigations into emerging immunotherapeutic strategies, such as immune cell engagers (ICEs) that work by promoting efficient tumor cell killing through the redirection of immune system against cancer cells. Most ICEs are bispecific antibodies that simultaneously recognize and bind to both cancer and immune cells generating an artificial synapse. Major side effects are cytokine release syndrome, hepatotoxicity, and neurotoxicity related to inappropriate immune system activation. Here, we provide a comprehensive overview of this compounds, the available preclinical and clinical evidence supporting their investigation and development in BC also highlighting the challenges that have prevented their widespread use in oncology. Finally, major strategies are explored to broaden their use in BC.