Antibody–drug Conjugates: Using Monoclonal Antibodies for Delivery of Cytotoxic Payloads to Cancer Cells

Abstract

One approach to improving activity of anticancer drugs is to conjugate them to antibodies that recognize tumor-associated, cell-surface antigens. The antibody–drug conjugate concept evolved following major advances, first, in the development of humanized and fully human antibodies; second, in the discoveries of highly cytotoxic compounds (‘drugs) linkable to antibodies; and finally, in the optimization of linkers that couple the drug to the antibody and provide sufficient stability of the antibody–drug conjugate in the circulation, optimal activation of the drug in the tumor, and the ability of the activated drug to overcome multidrug resistance. In this article, we will review the considerations for selecting a target antigen, the design of the conjugate, and the pre-clinical and clinical experiences with the current generation of antibody–drug conjugates.

Acknowledegments

The authors thank their colleagues, Tom Chittenden and John M Lambert for the critical reading of the manuscript.

Financial & competing interests disclosure

The authors are employees of ImmunoGen, Inc. and have stock options of ImmunoGen, Inc. (Victor Goldmacher currently does not own stock of ImmunoGen). Both authors are inventors in several patents and patent applications related to their employment at ImmunoGen. The authors have no other relevant affiliations or financial involvement with any other organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royaltes.

No writing assistance was utilized in the production of this manuscript.