https://phys.org/news/2018-10-flexible-stable-potent-cancernew-approach.html

The number of cytostatic drugs that have been successfully incorporated into such antibody conjugates has so far been limited. Researchers led by Hans-Georg Lerchen (Bayer AG) have now tried this with a cytotoxin that uses a different mechanism than classic cytostatic drugs for attacking the cell cycle. It is a novel pyrrole-based kinesin spindle protein (KSP) inhibitor. KSP plays a key role in centrosome separation during cell division. Blocking this step causes a strong antitumor effect. Even very low doses of the inhibitor were highly effective against a broad palette of cancer cell lines. Lerchen and his co-workers have demonstrated that this technique can be used to make highly active antibody conjugates. Use of different antibodies allows them to target a variety of types of tumor.

The researchers were able to connect the inhibitor at a variety of attachment points by stabile linkers to the antibody thereby hindering premature splitting. Only inside the tumor cells, the conjugates are metabolized by enzymes, releasing the inhibitor. Variation of the linker allows for controlled variation of the resulting inhibitor molecules so that their activity can be tailored to specific requirements. Inhibitors that cannot be expelled from the cells accumulate in the tumor cells, lengthening their active period. Inhibitors that can be expelled may enter neighboring tumor cells, which is especially useful in the treatment of tumors that contain a heterogenic pattern of antibody binding sites.