Unconjugated monoclonal antibodies (mAb) have revolutionized the treatment of many types of cancer. Some of these mAbs promote the clearance of malignant cells via direct cytotoxic effects. More recently, antibody-dependent cellular phagocytosis (ADCP) has been appreciated as a major mechanism of action for a number of widely-used mAbs, including anti-CD20 (rituximab, obinutuzumab), anti-HER2 (trazituzumab), and anti-CD38 (daratumumab). However, as a monotherapy these ADCP-inducing mAbs produce insufficient levels of cytotoxicity in vivo and are not curative. As a result, these mAbs are most effectively used in combination therapies. The efficacy of these mAbs is further hampered by the apparent development of drug resistance by many patients. Here we will explore the role of ADCP in cancer immunotherapy and discuss the key factors that could limit the efficacy of ADCP-inducing mAbs in vivo. Finally, we will discuss current insights and approaches being applied to overcome these limitations.
Unconjugated monoclonal antibodies (mAbs) have revolutionized the treatment of many types of cancer. Some of these mAbs promote the clearance of malignant cells via direct cytotoxic effects. More recently, antibody-dependent cellular phagocytosis (ADCP) has been appreciated as a major mechanism of action for a number of widely used mAbs, including anti-CD20 (rituximab, obinutuzumab), anti-HER2 (trastuzumab), and anti-CD38 (daratumumab). However, as a monotherapy, these ADCP-inducing mAbs produce insufficient levels of cytotoxicity in vivo and are not curative. As a result, these mAbs are most effectively used in combination therapies. The efficacy of these mAbs is further hampered by the apparent development of drug resistance by many patients. Here we will explore the role of ADCP in cancer immunotherapy and discuss the key factors that could limit the efficacy of ADCP-inducing mAbs in vivo. Finally, we will discuss current insights and approaches being applied to overcome these limitations.
Keywords: cancer; immunotherapy; macrophages; monoclonal antibodies; phagocytosis.