timsTOF Pro 2 for clinical proteomics
The Institutes for Research in Biomedicine (IRB) and Oncology Research (IOR) are well-known for their productive translational research in the fields of immunology and cancer. Recent achievements include the clinical implementation of more effective treatments for lymphoma patients (Rossi et al., New England Journal of Medicine 2022) and the development of FDA-approved clinical antibodies to treat SARS-CoV-2 patients (Pinto et al., Nature 2020).
In 2016, the IRB acquired a Q Exactive HF mass spectrometer to establish a proteomics platform that was used to identify binding targets of human monoclonal antibodies (Tan et al., Nature 2016; Chen et al., Nature 2020), and to identify immunogenic MHC-presented peptides derived from either pathogens or therapeutic antibodies (Cassotta et al., Journal of Experimental Medicine 2019 and Nature Medicine 2019). The platform was also used to characterize the proteomes of immune cells and engineered therapeutic bacteria (Canale et al., Nature 2021) and to study protein turnover in primary immune cells (Wolf et al., Nature Immunology 2020).
While the Q Exactive HF mass spectrometer continues to be a workhorse for several applications, its main limitation is its low sensitivity – a pertinent issue when analyzing clinical samples, which tend to be limited in quantity, and thus require a highly sensitive mass spectrometer to produce robust data of sufficient quality. Since our institutes are interested in the analysis of clinical samples, we propose to acquire a timsTOF Pro 2 instrument, which has proven to be a highly sensitive instrument suitable for clinical proteomics. This time-of-flight (TOF) mass spectrometer has an extremely high sequencing speed and an additional ion mobility dimension for improved data completeness and depth.
The timsTOF Pro 2 will be used to analyze proteomes from immune cells isolated from tumor metastases, cancer cells extracted from formalin-fixed-paraffin-embedded (FFPE) tissues by la-ser-capture microdissection, MHC peptidomes from primary dendritic cells that are rare and of utmost physiological importance, residual tumor cells of patient-derived xenografts leading to tumor relapse, and to perform structural proteomics. This instrument will provide us with the ability to explore the underlying cellular mechanisms of pathologies in a clinically-relevant setting and unprecedented manner. Furthermore, since no such instrument in southern Switzerland is currently available, it will strengthen our positions as centers for excellence in translational research here in Bellinzona.