Abstract
Antibody–drug conjugates (ADCs) are a family of targeted therapeutic agents for the treatment of cancer. ADC development is a rapidly expanding field of research, with over 80 ADCs currently in clinical development and eleven ADCs (nine containing small-molecule payloads and two with biological toxins) approved for use by the FDA. Compared to traditional small-molecule approaches, ADCs offer enhanced targeting of cancer cells along with reduced toxic side effects, making them an attractive prospect in the field of oncology. To this end, this tutorial review aims to serve as a reference material for ADCs and give readers a comprehensive understanding of ADCs; it explores and explains each ADC component (monoclonal antibody, linker moiety and cytotoxic payload) individually, highlights several EMA- and FDA-approved ADCs by way of case studies and offers a brief future perspective on the field of ADC research.
Highlights
Cytotoxic drugs are routinely used as part of traditional chemotherapy regimens for the treatment of different cancers
While such regimens can be effective for certain types of cancer, such as testicular cancer and Hodgkin lymphoma, the non-specific action of cytotoxic drugs means that rapidly dividing healthy cells are attacked as well as cancer cells, leading to the side effects commonly associated with chemotherapy such as hair loss, sickness and tiredness [1]
Subsequent advances in antibody, linker and payload technologies have driven the development of further antibody–drug conjugates (ADCs) with improved potency and serum half-lives, reduced immunogenicity and improved specificity for cancer cells compared to earlier efforts [6]
Summary
Cytotoxic drugs are routinely used as part of traditional chemotherapy regimens for the treatment of different cancers. The field of targeted therapy aims to find safer, more effective therapeutic agents by exploiting subtle differences between normal and cancer cells, and an example of this approach is seen in antibody–drug conjugates (ADCs). Rank amongst the most sophisticated pharmaceuticals ever developed, combining the cancer-targeting abilities of specialised antibodies with the cancer-killing abilities of cytotoxic drugs to selectively kill cancer cells [2]. Subsequent advances in antibody, linker and payload technologies have driven the development of further ADCs with improved potency and serum half-lives, reduced immunogenicity and improved specificity for cancer cells compared to earlier efforts [6].
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