An emerging playbook for antibody-drug conjugates: lessons from the laboratory and clinic suggest a strategy for improving efficacy and safety

Current Opinion in Chemical Biology
Penelope M Drake, David Rabuka

Abstract

Antibody-drug conjugates (ADCs) have become de rigueur for pharmaceutical oncology drug development pipelines. There are more than 40 ADCs undergoing clinical trials and many more in preclinical development. The field has rushed to follow the initial successes of Kadcyla™ and Adcetris™, and moved forward with new targets without much pause for optimization. In some respects, the ADC space has become divided into the clinical realm-where the proven technologies continue to represent the bulk of clinical candidates with a few exceptions-and the research realm-where innovations in conjugation chemistry and linker technologies have suggested that there is much room for improvement in the conventional methods. Now, two and four years after the approvals of Kadcyla™ and Adcetris™, respectively, consensus may at last be building that these two drugs rely on rather unique target antigens that enable their success. It is becoming increasingly clear that future target antigens will require additional innovative approaches. Next-generation ADCs have begun to move out of the lab and into the clinic, where there is a pressing need for continued innovation to overcome the twin challenges of safety and efficacy.

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Citations

Feb 20, 2016·Therapeutic Delivery·Mireille Vankemmelbeke, Lindy Durrant
Apr 6, 2016·Expert Opinion on Biological Therapy·Serengulam V GovindanDavid M Goldenberg
Oct 16, 2016·Protein & Cell·Kyoji Tsuchikama, Zhiqiang An
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Mar 5, 2016·Organic & Biomolecular Chemistry·Xi Chen, Yao-Wen Wu
Nov 10, 2017·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Penelope M Drake, David Rabuka
Sep 16, 2017·Angewandte Chemie·Dominik SchumacherChristian P R Hackenberger
Aug 20, 2017·Protein & Cell·William R Strohl
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May 10, 2017·Molecular Cancer Research : MCR·Aleksandra Sokolowska-WedzinaJacek Otlewski
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