Antibody-Drug Conjugate-Based Therapeutics: State of the Science.

Autor:	Birrer MJ; Division of Hematology-Oncology, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL., Moore KN; Stephenson Department of Obstetrics and Gynecology, Oklahoma Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, OK.; Sarah Cannon Research Institute, Nashville, TN., Betella I; Division of Hematology-Oncology, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL., Bates RC; Medical Affairs, ImmunoGen Inc., Waltham, MA.
Jazyk:	angličtina
Zdroj:	Journal of the National Cancer Institute [J Natl Cancer Inst] 2019 Jun 01; Vol. 111 (6), pp. 538-549.
DOI:	10.1093/jnci/djz035
Abstrakt:	Antibody-drug conjugates (ADCs) are complex engineered therapeutics consisting of monoclonal antibodies, directed toward tumor-associated antigens, to which highly potent cytotoxic agents are attached using chemical linkers. This targeted drug delivery strategy couples the precision of the antibody targeting moiety with the cytocidal activity of the payload, which is generally too toxic on its own to be systemically administered. In this manner, ADCs confer a means to reduce off-target toxicities in patients by limiting the exposure of normal tissues to the payload, thus broadening the potential therapeutic window compared with traditional chemotherapy. The pace of ADC development is accelerating, with the number of investigational agents in human trials having more than tripled over the past 5 years, underscoring the enthusiasm for this transformative approach to cancer treatment. Here, we review the key structural elements of ADC design (antibody, linker, and payload), highlighting critical aspects and technological advances that have affected the clinical effectiveness of this class of biopharmaceuticals. The ADC field continues to evolve, including ongoing efforts aimed at improving target selection, developing payloads with varied mechanisms of action and increased potency, designing innovative bioconjugation strategies, as well as maximizing efficacy and tolerability in patients. An overview of the current clinical trial landscape is provided, with emphasis on the clinical experience of the four ADCs to have received regulatory approval to date, as well as additional promising candidates currently in late-stage clinical development in both solid tumor and hematological malignancies. (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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