New agents activate immune cells against cancer
Two promising agents from the DKFZ-Bayer Research Alliance will be presented to an expert audience at this year's AACR Congress in Orlando. Both agents are designed to activate suppressed immune cells and thus support the immune defense against cancer. The annual congress of the American Association for Cancer Research (AACR) is considered the world's most important meeting for cancer research.
A few years ago, scientists from the DKFZ Brain Tumor Immunology Unit headed by Michael Platten discovered that degradation products of the amino acid tryptophan activate the aryl hydrocarbon receptor (AHR) in gliomas, malignant brain tumors. This activation has doubly fatal consequences: First, it directly affects tumor cells, fueling their proliferation and tissue invasion. Second, it enables the tumor to evade the immune system. Other cancers, such as leukemia and lymphoma, ovarian cancer and lung cancer, also constantly fire the AHR signaling pathway. This makes the receptor a promising target for novel cancer drugs.
In a strategic research collaboration between Bayer Health Care (Bayer) and Platten's research group, the scientists developed a selective AHR inhibitor that can be administered as a pill. This inhibitor has now been tested iby Bayer n a clinical trial in patients with advanced solid cancers.
The new substance has a dual effect on the immune system. On the one hand, it stimulates the protective cytotoxic T cells and dendritic cells. On the other hand, it blocks the harmful function of regulatory T cells and certain myeloid cells that suppress the immune response against cancer. Initial pharmacokinetics and biomarker results from the Phase I trial will be presented to an expert audience for the first time at the AACR meeting.
The second project from the DKFZ-Bayer Joint Immunotherapeutics Lab, which will be presented in Orlando, is also concerned with reactivating the stalled immune response against tumor cells. The research project was led by Rienk Offringa, director of the DKFZ-Bayer Joint Lab. Enzymes from the diacylglycerol kinase (DGK) family regulate intracellular signaling cascades that play an important role in T cell function. When diacylglycerol kinase zeta (DGKz) is inhibited, this reverses a signaling blockade. Activating signals that the cell receives via its T cell receptor can then be transmitted again and the T cell is ready for tumor defense.
DKFZ and Bayer have jointly developed a small-molecule substance that inhibits DGKz. Preclinical data on this new agent are now being reported for the first time at AACR. In addition, a phase I clinical trial with the new agent was initiated by Bayer last November.
In 2013, the German Cancer Research Center (DKFZ) and Bayer AG (Bayer) expanded their successful strategic research alliance in the search for novel cancer therapeutics by establishing a joint immunotherapy laboratory. The laboratory is located at DKFZ, and scientists from DKFZ and Bayer work in mixed teams to further develop new therapeutic approaches in the field of immuno-oncology.
With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.
To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany: