Antibody-Drug Conjugates: Targeting the Tumor Microenvironment

Antibody-drug conjugates (ADCs) have been used for more than two decades as tools for the selective delivery of cytotoxic agents to the tumor site, with the aim to increase anti-cancer activity and spare normal tissues from undesired toxicity. Until recently, most ADC development activities have focused on the use of monoclonal antibodies, capable of selective binding and internalization into the target tumor cells. However, in principle, it would be conceivable to develop non-internalizing ADC products, which liberate their toxic payload in the extracellular environment. In this Chapter, we review previous work performed on non-internalizing ADC products, with a special emphasis on drug conjugates which selectively localize to the modified extracellular matrix in the neoplastic mass.