Antibody–drug conjugates (ADCs) represent a groundbreaking advancement in cancer therapeutics, combining the high specificity of monoclonal antibodies with the potent cytotoxic effects of chemotherapy. This innovative approach aims to selectively target cancer cells while minimizing damage to healthy tissues, thereby overcoming the limitations of traditional chemotherapy.
ADCs are engineered molecules composed of three critical components: a monoclonal antibody that specifically binds to tumor-associated antigens, a cytotoxic payload capable of killing cancer cells, and a chemical linker that ensures the stability of the drug until it reaches the target. Upon binding to the target antigen on the surface of cancer cells, the ADC is internalized, and the cytotoxic drug is released intracellularly, leading to targeted cell death.
Clinically approved ADCs such as trastuzumab emtansine (T-DM1), targeting HER2 in breast cancer, and gemtuzumab ozogamicin, targeting CD33 in acute myeloid leukemia, have demonstrated substantial improvements in treatment outcomes, including enhanced progression-free survival and reduced systemic toxicity. These successes underscore the importance of precise antigen selection and the continuous evolution of ADC design strategies.
Despite their promise, ADC development is challenged by factors such as tumor antigen heterogeneity, multidrug resistance, and the need for stable yet cleavable linkers. However, advancements in antibody engineering, site-specific conjugation, and next-generation payloads are rapidly addressing these hurdles. Novel ADCs with bispecific targeting capabilities and innovative payload mechanisms are currently in development, further expanding their therapeutic potential.
This work emphasizes the role of HER2 and CD33-targeted ADCs as models of precision oncology, illustrating how these agents are redefining the landscape of chemotherapy. As research progresses, ADCs are expected to play an increasingly vital role in personalized cancer treatment, offering a powerful blend of specificity, efficacy, and safety.
