Conjugates of Small Molecule Drugs with Antibodies and Other Proteins

Biomedicines

Yang Feng¹  Zhongyu Zhu¹  Weizao Chen¹  Ponraj Prabakaran¹  Kedan Lin² 

[1]Protein Interactions Group, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA

[2] E-Mails:

[3]Genentech., San Francisco, CA 94080, USA

[4] E-Mail:

关键词: antibody-drug conjugates;    ADC;    biotherapeutics;    drugs;    biologics;   

DOI  :  10.3390/biomedicines2010001

来源: mdpi

【 摘 要 】

Conjugates of small molecule drugs with antibodies (ADCs) and with other proteins (protein-drug conjugates, PDC) are used as a new class of targeted therapeutics combining the specificity of monoclonal antibodies (mAbs) and other proteins with potent cytotoxic activity of small molecule drugs for the treatment of cancer and other diseases. A(P)DCs have three major components, antibody (targeting protein), linker and payload, the cytotoxic drug. Recently, advances in identifying targets, selecting highly specific mAbs of preferred isotypes, optimizing linker technology and improving chemical methods for conjugation have led to the approval of two ADCs by Food and Drug Administration (FDA) and more than 30 ADCs in advanced clinical development. However, the complex and heterogeneous nature of A(P)DCs often cause poor solubility, instability, aggregation and eventually unwanted toxicity. This article reviews the main components of A(P)DCs, and discusses the choices for drugs, linkers and conjugation methods currently used. Future work will need to focus on developments and strategies for overcoming such major problems associated with the A(P)DCs.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.