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Antibody-drug conjugates for cancer therapy
journal contributionposted on 2020-11-23, 06:05 authored by Umbreen HafeezUmbreen Hafeez, Sagun ParakhSagun Parakh, Hui GanHui Gan, Andrew ScottAndrew Scott
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Antibody–drug conjugates (ADCs) are novel drugs that exploit the specificity of a monoclonal antibody (mAb) to reach target antigens expressed on cancer cells for the delivery of a potent cytotoxic payload. ADCs provide a unique opportunity to deliver drugs to tumor cells while minimizing toxicity to normal tissue, achieving wider therapeutic windows and enhanced pharmacokinetic/pharmacodynamic properties. To date, nine ADCs have been approved by the FDA and more than 80 ADCs are under clinical development worldwide. In this paper, we provide an overview of the biology and chemistry of each component of ADC design. We briefly discuss the clinical experience with approved ADCs and the various pathways involved in ADC resistance. We conclude with perspectives about the future development of the next generations of ADCs, including the role of molecular imaging in drug development.
This review was supported in part by grants from NHMRC (No. 1092788), the Cancer Council of Victoria (No. 1164229) and the Operational Infrastructure Support Program provided by the Victorian Government and is acknowledged. Andrew Scott is supported by an NHMRC Investigator Fellowship (No. 1177837).
Rights StatementThe Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.
Science & TechnologyLife Sciences & BiomedicinePhysical SciencesBiochemistry & Molecular BiologyChemistry, MultidisciplinaryChemistryantibody–drug conjugateADCmonoclonal antibodycytotoxic payloadlinkerscancermolecular imagingACUTE MYELOID-LEUKEMIAPROMISING ANTITUMOR EFFICACYTRASTUZUMAB EMTANSINE T-DM1CELL MATURATION ANTIGENGEMTUZUMAB OZOGAMICINBRENTUXIMAB VEDOTINOPEN-LABELMULTIPLE-MYELOMAHODGKIN LYMPHOMAINTRACELLULAR TRAFFICKINGantibody–drug conjugatelinkers, cancermolecular imaging.Organic Chemistry