For most patients, chemotherapy is still the standard course of treatment, and while the approach is quite efficient, it does present a number of adverse effects – nausea, hair loss, exhaustion etc. This is why Dr. Hans-Georg Lerchen, principal scientist in Bayer’s Pharmaceuticals Division is currently working on alternative solutions.
Antibody-drug conjugates (ADCs for short) work on the basis of the Trojan Horse principle, they track down tumor cells and plant a “payload” directly inside them. In theory, their structure is pretty simple: take one small drug molecule and connect it to an antibody using a linker. The antibody attaches itself to certain binding sites (antigens) that are particularly numerous on the surfaces of targeted tumor cells. The drug is absorbed through the walls of the abnormal cell and then released, destroying the cancer from within.
Along the way, there have been many challenges. The number of successfully incorporated antibodies has been so far limited, forcing the team to look for novel options. Recently they have started using a pyrrole-based kinesin spindle protein (KSP) inhibitor which has proven to be highly effective against a broad palette of cancer cell lines.
The binding compound similarly plays a crucial role in the process. The linker “must remain stable in the blood circulation, as otherwise the cell toxin could be released too soon”, and at the same time “must be able to be cleaved later inside the lysosomes within the tumor cells so that the cell toxin can exert its action there”.
These conjugates have shown remarkable performance both with in vitro and in vivo testing. Mouse experiments have led to complete remission of a human bladder tumor model.
Overall, the procedure offers many advantages over the current course, it’s highly targetable, more flexible in terms of possible drugs and much safer as surrounding healthy cells remain unharmed.