Recent advances in T-cell based immunotherapy have raised hopes for curative treatments, capable of eliminating the cancer cell. A key requirement for targeted immunotherapy is the identification of antigens that are present in tumor cells but absent in healthy cells. These antigens are mutated parts of proteins present in the tumor cells of the patient. Traditionally, tumor antigen identification has been limited by either high costs or low sensitivity depending on the implemented methodology.
In this study, spearheaded by scientists at CeMM Research Center for Molecular Medicine in collaboration with researchers from the Medical University of Vienna and the University of Pavia, a novel RNA-based methodology has been developed for the systematic identification of cancer antigens for each patient. Fiorella Schischlik, first author of the study and PhD student at CeMM; reflects: "As a bioinformatician, with a particular interest in data analysis, I was excited to find how much useful information can be extracted from a single RNA sequencing data set."
Using RNA sequencing performed on the tumor biopsy as a basis for target discovery is particularly efficient. First, only targets are identified that are expressed and therefore relevant and second, a variety of different mutation classes can be addressed. Fusions and splicing-related aberrations are examples of mutation classes, where RNA sequencing is the preferred method of their systematic discovery. In this study, the researchers were able to demonstrate that especially patients with mutations in the splicing factor SF3B1 and CALR genes produce a variety of tumor specific peptides. These altered peptides could serve as a blueprint for cancer vaccine production.
Robert Kralovics, Principal Investigator at CeMM and corresponding author of the study is excited to start the next step in target validation: "We want to show that these tumor-specific antigens are capable of eliciting an immunogenic response in the patients and are, therefore, suitable to serve as bona fide targets for T-cell directed killing of the cancer cell. Finding immunotherapy targets in 62% of MPN patients – as a conservative estimation - is raising hope that many MPN patients might benefit from this approach."
The study "Mutational Landscape of the Transcriptome Offers Putative Targets for Immunotherapy of Myeloproliferative Neoplasms" has been published in Blood.
Authors: Fiorella Schischlik, Roland Jäger, Felix Rosebrock, Eva Hug, Michael Schuster, Raimund Holly, Elisabeth Fuchs, Jelena D. Milosevic Feenstra, Edith Bogner, Bettina Gisslinger, Martin Schalling, Elisa Rumi, Daniela Pietra, Gottfried Fischer, Ingrid Faé, Loan Vulliard, Jörg Menche, Torsten Haferlach, Manja Meggendorfer, Anna Stengel, Christoph Bock, Mario Cazzola, Heinz Gisslinger and Robert Kralovics
The Study was funded by the Austrian Science Fund (FWF) and the Associazione Italiana per la Ricerca sul Cancro.
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences seeks to achieve maximum scientific innovation in molecular medicine to improve healthcare. At CeMM, an international and creative team of scientists and medical doctors pursues free-minded basic life science research in a large and vibrant hospital environment of outstanding medical tradition and practice. CeMM’s research is based on post-genomic technologies and focuses on societally important diseases, such as immune disorders and infections, cancer and metabolic disorders. CeMM operates in a unique mode of super-cooperation, connecting biology with medicine, experiments with computation, discovery with translation, and science with society and the arts. The goal of CeMM is to pioneer the science that nurtures the precise, personalized, predictive and preventive medicine of the future. CeMM trains a modern blend of biomedical scientists and is located at the campus of the General Hospital and the Medical University of Vienna. www.cemm.at
Medical University of Vienna - short profile
Medical University of Vienna (MedUni Vienna) is one of the most traditional medical education and research facilities in Europe. With almost 8,000 students, it is currently the largest medical training centre in the German-speaking countries. With 5,500 employees, 26 departments and three clinical institutes, 12 medical theory centres and numerous highly specialised laboratories, it is also one of Europe's leading research establishments in the biomedical sector.