Monoclonal Antibody-Based Cancer Therapy: From Mechanistic Insights to Clinical Practice

Abstract

Monoclonal antibodies (mAbs) are a cornerstone of cancer therapy. They offer high target specificity and diverse cytotoxic mechanisms, which render them superior to many conventional cytotoxic treatments. This review examines therapeutic mAbs from two aspects. First, their mechanisms of action are analysed, including direct target modulation (signaling inhibition and ADC payload delivery), Fc‑mediated effector functions (ADCP, ADCC, and CDC), and immune checkpoint blockade (CTLA-4, PD-1/PD-L1, LAG-3, and TIM-3 pathways). In addition, engineering strategies that potentiate these effects are considered as well, such as Fc modification and optimised linker‑payload design for antibody-drug conjugates. Second, the clinical landscape of approved mAbs is reviewed. Their remarkable success in hematologic malignancies (anti-CD20, anti-CD33, anti-CD38) are compared with the greater challenges in solid tumors, where tumour heterogeneity, immunosuppressive microenvironments and primary resistance frequently limit therapeutic efficacy. In solid tumours, biomarker-driven agents (anti-HER2, anti-EGFR) and immune checkpoint inhibitors are central. Immune-related adverse events also represent an important safety concern for checkpoint-blocking antibodies. It is critical to understand these mechanisms and clinical outcomes before optimizing current therapies and guiding next-generation antibody development, including novel ADCs and bispecific antibodies.