Antibody drug conjugates represent one of the most exciting new developments in cancer therapy in recent years. Building on over 30 years of research in academia and the pharmaceutical industry, the recent approval of several ADC’s heralds the beginning of a new era in targeted cancer therapy. Today there are nearly 100 ADC’s in clinical development against a wide variety of different cancer types.
Antibody drug conjugates consist of three components, each of which have been highly optimized for delivery of a therapeutic effect at the desired site of action. The monoclonal antibody is the end-product of extensive screening designed to identify a delivery vehicle with a high degree of specificity for a unique antigen over-expressed on tumor cells. The antibody carries with it a highly potent cytotoxin which is delivered intracellularly to the tumor once the antibody internalizes upon binding the target antigen. Historically cytotoxins have typically fallen into one of two classes: microtubule polymerization inhibitors that inhibit the ability of rapidly growing tumor cells to divide and DNA intercalating agents which introduce lethal double strand breaks in the DNA of the target tumor cell. However, the rate of innovation over the last several years has witnessed an expansion of new cytotoxins with different biological actions and the opportunity to widen the therapeutic window for patients. The last component is the linker chemistry which attaches the cytotoxic payload to the monoclonal antibody. Linkers have been developed to be stable in the blood stream and to allow for the efficient release of the payload once inside the target cell.
Ardeagen utilizes a variety of linker-payload combinations to identify the best combination for a given therapeutic target.