Antibody-Drug Conjugates as Therapeutic Agents in Oncology: Overview And Perspectives
Pp. 139-189 (51)
Milos Dokmanovic, Mohammed K. ElZarrad, Dianne S. Hirsch and Wen J. Wu
Antibody-drug conjugates (ADCs) are an emerging class of therapeutics that
are generated by covalent attachment of cytotoxic agents to monoclonal antibodies via
linkers. It is generally believed that following antibody binding to the antigen and ADC
internalization, release of toxic payload would produce cytotoxic effects in tumor cells
in relatively selective manner. The clinical development of ADCs was not feasible until
several critical prior developments took place, including development of recombinant
therapeutic monoclonal antibody production, advancement of linker technology, and
discovery of potent cytotoxic agents.
In this book chapter, we will briefly introduce the history of ADC development and
focus on the development and mechanisms of action of ADCs in oncological
indications. In addition to covering present ADC therapies in clinical trials we will also
offer possible future directions for ADC therapies, such as development of antibodies
against new therapeutic targets, use of novel antibody and non-antibody-based
platforms for the ADC development, use of novel linker designs for ADC generation, as
well as development of novel payloads for antibody-based conjugates. As these
development trends continue, future potential of ADC therapies to address the needs in
oncology indications will be explored. Note that the information presented in this article
represents publically available information. Any opinions expressed reflect the views of
the authors and do not represent the policy of the U.S. Food and Drug Administration.
Antibody-drug conjugates, ADC, oncology, antibody, linker, payload,
Division of Monoclonal Antibodies, Office of Biotechnology Products, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Bethesda, Maryland, USA.