Rhine-Region Serenity to Find Treatments
Despite great progress through modern medicine, cancer is still the second most common cause of death. Working on antibody-drug conjugates, Dr. Hans-Georg Lerchen is trying to reduce the harsh side effects of chemotherapy and improve its impact at the same time.
Losing a friend or seeing him or her suffer from cancer is a tragic experience. Unfortunately, many people know this situation since cancer is the cause of every sixth death worldwide. Our research team is working to change this statistic. We’re working on the development of a special form of chemotherapy called antibody-drug conjugates (ADCs). Normally, chemotherapy is associated with strong side effects including loss of immune-system defense, exhaustion, nausea, and hair loss. We’re trying to soothe those adverse effects by targeting tumor cells with higher precision and thus protect healthy tissue.
The idea behind our targeted chemotherapy approach can be compared to the legend of the Trojan horse. We bring a drug to the tumor by packing it onto an antibody that selectively finds and infiltrates malignant cells. After entering the tumor cell, the antibody releases the drug, which now, within the tumor, unleashes its power.
Simple Idea, Difficult Implementation
However, converting this concept into reality isn’t as easy as it sounds. Because many things have to work together properly, we have to adjust a range of parameters. The key to recognizing the tumor cell is the antibody. It’s shaped like the letter Y, with two arms that can attach to a target on the tumor cell’s surface. Depending on its origin, each tumor has a different shape. So we have to adjust the antibody, and its arms, for each individual type of tumor. The properties in the two other components of the ADC, the linker (the connecting element between the antibody and the active agent) and the payload (explain in brief), also have to be adapted to the antibody and its target. And every change in chemical structure may have an impact on the composition and its function as a whole.
Because of the challenge involved, a lot of people with different kinds of expertise are involved in the research we do at the Bayer sites in Wuppertal, Berlin, Cologne and San Francisco. In my role, as a chemist, I have to find the right combination of drug and linker. And while I’m a passionate chemist, understanding biological processes and using chemical molecules to intervene in them is even more interesting to me.
Learning from Sports
Science is fascinating, but it’s linked with frustrating setbacks. You have to accept failure, draw conclusions and start over again with strong motivation and the will to continue. As a long-time fan of the German soccer club FC Cologne, I see a lot of parallels. Sometimes the season goes well for the team; sometimes it doesn’t. But in the end, everything can turn out fine if the team keeps going. It’s not helpful to think too much about a lost game – that’s my Rhine-region mentality, I suppose.
Sports are not just a good comparison to my work – they’re also my to relax. I love skiing and biking, especially with my wife and my four children. After a couple of years playing handball, I switched over to (German) football. Today, I play for fun, not competitively. At age 58, I’m not even the oldest guy in the team. But sometimes – and this is the same as with science – experience should not be underestimated.
CV Hans-Georg Lerchen
|1959||born in Hoehr-Grenzhausen, Germany|
|1987||PhD in Organic Chemistry at University of Mainz, Germany|
|1987-1988||Post Doctoral work: Max Planck Institute (MPI) grant at the MPI for Biochemistry Research, Munich, Germany|
|1988-2002||Bayer AG, Central Research, Leverkusen, Germany|
|2002-today:||Bayer AG, Pharmaceuticals Division, Medicinal Chemistry, Wuppertal, Germany|
Antibody-Drug Conjugates with Pyrrole-Based KSP Inhibitors as the Payload Class
Angewandte Chemie, International Edition, 2018, 57, No. 46
Hans-Georg Lerchen, Sven Wittrock, Beatrix Stelte-Ludwig, Anette Sommer, Sandra Berndt, Nils Griebenow, Anne-Sophie Rebstock, Sarah Johannes, Yolande Cancho-Grande, Christoph Mahlert, Simone Greven, Carsten Terjung.
Preclinical Antitumor Efficacy of BAY 1129980 – a Novel Auristatin-Based Anti-C4.4A (LYPD3) Antibody–Drug Conjugate for the Treatment of Non–Small Cell Lung Cancer.
Molecular Cancer Therapeutics, 16 May 2017.
Jörg Willuda, Lars Linden, Hans-Georg Lerchen, Charlotte Kopitz, Beatrix Stelte-Ludwig, Carol Pena, Claudia Lange, Sven Golfier, Christoph Kneip, Patricia E. Carrigan, Kirk Mclean, Joachim Schuhmacher, Oliver von Ahsen, Jörg Müller, Frank Dittmer, Rudolf Beier, Sherif El Sheikh, Jan Tebbe, Gabriele Leder, Heiner Apeler, Rolf Jautelat, Karl Ziegelbauer and Bertolt Kreft.
Design and Optimization of 20-O-Linked Camptothecin Glycoconjugates as Anticancer Agents.
Journal of Medicinal Chemistry, 2001, Vol. 44, No. 24.
Hans-Georg Lerchen, Joerg Baumgarten, Karsten von dem Bruch, Thomas E. Lehmann, Michael Sperzel, Grazyna Kempka and Heinz-Herbert Fiebig.
Lectin-Mediated Drug Targeting: Discrimination of Carbohydrate-Mediated Cellular Uptake between Tumor and Liver Cells with Neoglycoconjugates Carrying Fucose Epitopes Regioselectively Modified in the 3-Position.
Angewandte Chemie, International Edition, 1999, 38, No. 24.
Hans-Georg Lerchen, Joerg Baumgarten, Norbert Piel, and Victoria Kolb-Bachofen.
Preparation of antibody-KSP inhibitor conjugates for treating hyperproliferative and angiogenic diseases (2015).
WO 2015096982 A1
Preparation of alkylaminodicyanopyrididines as adenosine receptor antagonists (2010).
WO 2010086101 A1
Preparation of carbohydrate-modified cytostatic agents (1996).
DE 19512484 A1