Mechanisms of Resistance to Monoclonal Antibodies (mAbs) in Lymphoid Malignancies

摘要: Passive immunotherapy with therapeutic monoclonal antibodies (mAbs) has revolutionized the treatment of cancer, especially hematological malignancies over last 20 years. While use mAbs improved outcomes, development resistance is inevitable in most cases, hindering long-term survival cancer patients. This review focuses on available data mechanisms to rituximab and includes some additional information for other currently malignancies. Mechanisms have been identified that target all described mAb activity including altered antigen expression or binding, impaired complement-mediated cytotoxicity (CMC) antibody-dependent cellular (ADCC), intracellular signaling effects, inhibition direct induction cell death. Numerous approaches circumvent continue be investigated, but a thorough understanding which are clinically relevant still elusive. In recent years, deeper tumor microenvironment targeting apoptotic pathway led promising breakthroughs. Resistance may driven by unique patient-, disease-, antibody-related factors. Understanding will guide strategies overcome re-sensitize cells these biological agents.