To more efficiently treat breast cancer, scientists have been researching molecules that selectively bind to cancer cells and deliver a substance that can kill the tumor cells, for several years. Researchers from the University and University Hospital Basel have now for the first time successfully combined such an antibody-drug conjugate with a therapy that stimulates the immune system to attack tumor cells. This opens the door to new therapeutic options in the treatment of breast cancer, report the researchers in the scientific journal Science Translational Medicine.
In nearly every fifth breast cancer patient, an above-average number of HER2 receptors are located on the surface of the tumor cells. These receptors are molecules that send growth factor signals into the cell. The overabundance of receptors causes the cancer cells to divide rapidly and the tumor grows faster than average.
For some years now, a new class of drugs called antibody-drug conjugates (ADCs) have been used, which work in two ways: they consist of an antibody that binds selectively to the tumor cell receptor and interrupts the signal to propagate; they also act as a transport vehicle for a chemical substance that enters the cancer cells with the antibody and triggers their death. The researchers demonstrate that the use of specific cytotoxic substances can also have a beneficial effect on the body’s immune system.
Combination with immunotherapy
Researchers, led by Prof. Alfred Zippelius at the Department of Biomedicine, from the University and University Hospital Basel have now gone one step further: in a pre-clinical study performed in mouse breast cancer models, they combined the ADC ‘trastuzumab emtansine’ with an additional immunotherapy that activates the immune system into attacking tumors more efficiently.
They focused on what is known as immunoregulatory checkpoints. These are receptors on immune cells, which control for example effector T-cells by dampening their activation if damage to healthy cells is imminent. By administering a complementary antibody, they blocked the function of two such immune checkpoints, whereby different types of endogenous T-cells were activated.
On its own, this immune response had no immediate effect in the fight against the utilized breast tumors, but in combination with the ADC it proved itself effective in attacking cancer cells in mice, resulting in the complete cure of the majority of mice receiving the combination therapy.
The researchers were also able to further demonstrate that regulatory T-cells play a host protective role in this therapeutic setting. Their removal resulted in excessive inflammation and tissue damage.
“Our results clearly demonstrate that antibody-drug conjugates are suitable for use in a combination therapy, opening new perspectives for the treatment of breast cancer,” says lead author Dr. Philipp Müller on the significance of the study.
Philipp Müller, Matthias Kreuzaler, Tarik Khan, Daniela S. Thommen, Kea Martin, Katharina Glatz, Spasenija Savic, Nadia Harbeck, Ulrike Nitz, Oleg Gluz, Michael von Bergwelt-Baildon, Hans Kreipe, Sai Reddy, AQ Matthias Christgen, Alfred Zippelius
Trastuzumab emtansine (T-DM1) renders HER2+ breast cancer highly susceptible to CTLA-4/PD-1 blockade
Science Translational Medicine (2015), doi: 10.1126/scitranslmed.aac4925
Prof. Dr. Alfred Zippelius, University of Basel/University Hospital of Basel, Department of Biomedicine, tel. +41 61 265 23 55, email: firstname.lastname@example.org
Dr. Philipp Müller, University of Basel/University Hospital of Basel, Department of Biomedicine, tel. +41 61 265 23 55; +41 61 556 52 21, email: email@example.com
Reto Caluori | Universität Basel
When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie
WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
23.03.2017 | Life Sciences
23.03.2017 | Power and Electrical Engineering
23.03.2017 | Earth Sciences