Affiliation:
1. ImmunoGen, Inc., 830 Winter Street, Waltham, MA 02451-1477, USA
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.
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