A pathway to personalized immunotherapy against breast cancer

Dortmund, December 2019 ++++

I³-STM dealt with a new, tailor-made immunotherapeutic approach using small antibody mimetics synthesized for the therapy of triple-negative breast cancer (TNBC), which is still insufficiently treated with the classic methods. These drugs consist of components that stimulate the immune system and recognize tumor-specific marker molecules on the tumor parenchyma and the stroma. In addition, the search for biomarkers in the tumor parenchyma and stroma, as well as in blood, enables the establishment of tailored drugs that focus on marker expression and immune activation for TNBC patients.

The EU and the state of North Rhine-Westphalia have supported a consortium of three companies and three academic institutions with 3 million euros in pursuing a new type of immunotherapeutic approach to particularly aggressive, triple negative breast cancer. A characteristic of this type of tumor, which occurs in about 15 percent of all breast cancer cases, is the lack of estrogen as well as progesterone and HER2 / neu receptors. SABs (small synthetic antibodies), the active pharmaceutical ingredients of Syntab Therapeutics GmbH from Würselen, recognize specific marker molecules on tumor cell surfaces and have effector components that stimulate the patient’s own immune system. These drugs are supposed to enable the immune system to turn itself against the disease, the humoral immune response producing specific anti-tumor antibodies.

Part of the project was to search for biomarkers that would allow tailoring new mini-antibody drugs, like those developed by Syntab Therapeutics, to patients as personalized medicine. “We have been able to show a good efficacy of one compound. The drug will now take further development stages until we find a strong partner for the expensive advanced clinical trials, “explains the Project Manager Ute Steinbusch, CEO of Syntab Therapeutics.

These complex drug molecules which are composed of two cyclic peptides, a polyethylene glycol linker and an effector peptide, were successfully synthesized at Taros Chemicals in Dortmund. Computer-aided drug design (CADD) and molecular modeling enabled to calculate new SABs and to define them as target molecules for laboratory syntheses and to produce them by using parallel solid-phase synthesis in amounts of 1 g.

Moreover, TECOdevelopment GmbH from Rheinbach has developed various tests to analyze the formation of unwanted antibodies after drug administration. Gremse-IT GmbH from Aachen has developed software for image reconstruction and evaluation, which was evaluated and used by the Institute of Experimental Molecular Imaging of the RWTH Aachen under Prof. Twan Lammers for non-invasive studies on the biodistribution of the drug molecule. The research groups of Prof. Frank Tacke and Adj. Professor Dr. Julia Steitz from the RWTH Aachen University Hospital were responsible for achieving the project goals and played a key role in presenting the efficacy of the new drug molecule.