The very first antibody-drug conjugates (ADCs) to enter clinical evaluation sought to improve the therapeutic index of approved anti-cancer drugs, such as doxorubicin and vinblastine, by linking them to tumor-selective monoclonal antibodies. However, clinical failure of these early ADCs dampened enthusiasm for this approach. The realization that antibodies could only bind to a limited number of antigens on a tumor cell surface necessitated the development of highly potent cytotoxic drugs.
The incorporation of highly potent drugs, or payloads, into ADCs led to the FDA approval of four ADCs in the first 30 years of clinical testing. Subsequently, more careful selection of targets, linkers, and payloads has revolutionized the field with eight ADCs approved by the FDA in the last five years. In this Learning Lab, Ravi Chari, PhD, will give his take on currently approved ADCs on the market, their mechanisms of action, clinical relevance, and learnings in their development.
He will discuss the properties of the 12 FDA-approved ADCs, with emphasis on the selection of the three ADC components: the antibody, linker, and payload..
