Mainz, Germany, April 18, 2018 – Ugur Sahin, Scientific Director at TRON, has been awarded one of the prestigious ERC Advanced Grants 2017 for his project ‘SUMMIT - Stepping Up mRNA Mutanome Immunotherapy’, totaling 2.5 Million Euros over 5 years.
The ERC Advanced Grants are awarded to well-established, leading principal investigators to pursue ground-breaking projects. SUMMIT is one of the 269 projects proposed for funding out of 2,167 submitted proposals within the 2017 application round.
Read more about the ERC Advanced grants and see the complete list of awardees here.
Insight into the human HLA expression pattern opens up new ways of improving cancer vaccine development
The human leukocyte antigen system (HLA system) is a group of genes that are central to the function of the immune system. These protein complexes can be found either on almost all cells (HLA class I complex) or on specific, professional antigen-presenting cells (HLA class II complex) and serve to present antigen to T cells. There is increasing evidence that pathogenic cells produce HLA class I and class II molecules either poorly or not at all, in order to escape elimination by the immune system. Recent research by bioinformaticians at TRON provides new insights into cell defense mechanisms that might assist cancer cells in evading detection by the immune system.
Functional extension of the existing seq2HLA algorithm
"Our seq2HLA algorithm, published in 2015, uses standardized NGS expression data (RNA-Seq) and gives the most likely HLA class I and II locus-specific gene expression," says Sebastian Boegel, first author of the recently published article in the journal BMC Medical Genomics. "We have now functionally expanded the algorithm so that we can now also determine non-classical HLA types and their gene expression." In addition, the research team has determined the expression profiles of two types of proteasome (constitutive vs. immunoproteasome) of the different tissues and additionally correlated these with HLA expression. "To the best of our knowledge, the present work provides for the first time a comprehensive expression atlas of HLA class I (classical and non-classical) and class II gene loci."
Specific interaction of the overall components is crucial
"Our results not only shed light on the cell type-specific HLA expression patterns, but also show extremely variable gene expression of the basic components of antigen processing and presentation in different cell types," continues Sebastian Boegel. "The data suggest that a specific interaction between the components involved in antigen processing could be crucial to maintain tolerance in immune-privileged tissues, which in turn prevents immune-related diseases."
Comprehensive expression atlas for a better understanding of immune diseases
"We assume that this newly published resource will be the starting point for new approaches in cancer research," continues Martin Löwer, head of the bioinformatics unit at TRON. The expression atlas could be of interest e.g. when HLA dysregulation in tumor cells is studied as part of their immune defense mechanisms, or even for the selection of new target structures for cancer immunotherapy. "Above all, the strong tissue-restrictive physiological expression and its immunosuppressive functions of HLA-G makes this an interesting molecule in cancer research," concludes Martin Löwer.
HLA Class I and Class II Expression Body Map. NGS RNA Seq data from physiological human tissues are analyzed using the seq2HLA algorithm to determine the classical HLA class I (blue) and HLA class II (red) expression profiles.
Mainz, March 23, 2018 – TRON is delighted to announce a review authored by Ugur Sahin and Özlem Türeci in the journal Science.
“Personalized vaccines for cancer immunotherapy” outlines the genetic basis for why almost every cancer is unique, and how with innovations in mutation mapping, target validation and vaccine production, it is possible to design and provide to patients, in time, the first truly personalized treatments for cancer.
You can read this overview of a fast-moving and exciting field here.
Mainz, March 2018 – On March 15th, Prof. Dietmar Zehn from the Technical University of Munich, School of Life Sciences Weihenstephan, will be visiting Mainz in the context of our Seminars in Translational Oncology series (SITO). You are cordially invited to his talk at 5 pm in building 708 of the University Medicine Mainz.
The title of his talk is:
Subsets and T cell differentiation in chronic LCMV infection
The presentation is open to everybody.
Prof. Dietmar Zehn is a professor of Animal Physiology and Immunology. He earned a MD/PhD degree from the Humboldt University in Berlin in 2004, for having published papers on the antigen presenting capacity of dendritic cells. In the same year, he became a post-doctoral fellow of Michael J. Bevan in the Department of Immunology at the University of Washington in Seattle, USA. There he investigated how the affinity of T cell receptors (TCR) for self- and foreign-peptide MHC-complexes impacts T cell responses. His key findings are that central and peripheral tolerance routinely fail to eliminate low affinity autoimmune T cells and that even very low affinity TCR and peptide-MHC interactions are sufficient to generate effector and memory T cells. His excellent expertise in the fields of immunology of infectious diseases, immunological self-tolerance, and cellular immunology has led to important scientific contributions.
His publication list can be viewed following this link.
Mainz, February 16, 2018 – The Keystone Symposium on Antibodies as Drugs: Translating Molecules into Treatments, will take place February 25th – March 1st, 2018 at the Whistler Conference Centre in Whistler, Canada.
Ugur Sahin will speak in the session on Novel Ways to Deliver Antibody Therapy on Thursday, March 1. The title of his lecture is “Antibody and mRNA-based Therapeutics”.
For more information on this event, please see the official Keystone website.
We are pleased to announce a three-year grant from the Falconwood Foundation, New York, USA, totalling 3 Million Euros. The grant supports the launch of a new research project to identify biomarkers specific for neuroendocrine tumors (NETs) that are crucial for the development of new, personalized immunotherapies to treat NET patients.
Further details are announced in the official press release.
TRON in the Media
Welcome to TRON
TRON – Translational Oncology at the University Medical Center of the Johannes Gutenberg University Mainz is a biopharmaceutical research organization that pursues new diagnostics and drugs for the treatment of cancer and other severe diseases with high medical need. A focus of TRON is the development of novel platforms for individualized therapies and biomarkers, translating basic research into drug applications. TRON partners with academic institutions, biotech companies and the pharmaceutical industry, executing research with leading-edge technologies and supporting the development of innovative drugs to promote human health.