Immunotoxins and Anticancer Drug Conjugate Assemblies: The Role of the Linkage between Components

Toxins

Franco Dosio¹  Paola Brusa² 

[1] Department of Drug Science and Technology, University of Torino, Torino 10125, Italy;

关键词: immunotoxin;    antibody drug conjugate;    linker;    conjugation process;    toxins;    anticancer agents;   

DOI  :  10.3390/toxins3070848

来源: mdpi

【 摘 要 】

Immunotoxins and antibody-drug conjugates are protein-based drugs combining a target-specific binding domain with a cytotoxic domain. Such compounds are potentially therapeutic against diseases including cancer, and several clinical trials have shown encouraging results. Although the targeted elimination of malignant cells is an elegant concept, there are numerous practical challenges that limit conjugates’ therapeutic use, including inefficient cellular uptake, low cytotoxicity, and off-target effects. During the preparation of immunoconjugates by chemical synthesis, the choice of the hinge component joining the two building blocks is of paramount importance: the conjugate must remain stable in vivo but must afford efficient release of the toxic moiety when the target is reached. Vast efforts have been made, and the present article reviews strategies employed in developing immunoconjugates, focusing on the evolution of chemical linkers.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.