Checkpoint inhibitors are antibodies which are intended to prevent manipulation of the immune system by tumour cells.
To prevent over-reactions of the immune system (T-lymphocytes), the immune system has a number of mechanisms. Tumours misuse these immune control points or checkpoints in order to override the immune defence against them.
The activation of PD-1 (“programmed cell death”) triggers apoptosis in T-lymphocytes. The PD-1 receptor, which sits on the surface of the T cells, is activated by the binding of the ligands PD-L1 and PD-L2 (“programmed cell death ligand”) on tumour cells and thereupon suppress the immune cells which attack cancer cells. The cancer cell thus escapes the cytotoxic immune reaction.
With antibody therapies these bonds are to be prevented so that the immune cells can attack the cancer cells.
In the IOZK in Cologne, these therapies are combined with other modern therapies. The goal is that the immune system actually recognises the tumour cells, a prerequisite for the therapies to show success with modern checkpoint inhibitors. A great deal of effort is made at IOZK, which has its price.
Dr. Wilfried Stücker has approached Zyagnum AG to jointly develop a test that can detect PD-1 and the ligands PD-L1 and PD-L2. Only when these ligands are expressed by tumour cells does therapy with the appropriate checkpoint inhibitors make sense. Against the background of the high costs involved in such modern therapy forms, a diagnostic is necessary which allows targeted therapies to be implemented. Unfortunately, therapies with checkpoint inhibitors also show unpleasant and debilitating side effects, another reason to use them only if the prerequisites for effectiveness can be fulfilled.