Beyond the described roles for proteomics in target discovery approaches, specialized applications of MS-based proteomics in surfaceome, secretome, and immunopeptidomics are important for drug discovery. Proteins involved in intercellular communication, such as cell surface-exposed receptors or ligands, represent targets for antibodies and small molecule inhibitors to manipulate cellular crosstalk or signaling cascades. Moreover, surface-exposed immunogenic host or microbial proteins function as antigens and therefore proteomics lends itself to the discovery of vaccine candidates.
Proteomic strategies have been used in combination with the enrichment and identification of surface-exposed proteins e.g. based on glycosylation or biotin labeling. Moreover, secretome analysis by MS can identify proteins associated with cellular communication and suggest novel avenues for the design of host- and pathogen-directed therapeutic options. The interface between host cells and pathogens is a rapidly advancing research area with potential for drug discovery. For example, pathogen protein secretion upon host-stimulation or secreted proteins from tumor cells can be enriched and identified, serving as diagnostic and therapeutic biomarkers.
The field of immunopeptidomics focuses on peptides derived from host and/or microbial proteins, which are presented by the human leukocyte antigens (HLA), also known as the major histocompatibility complex (MHC), and are decisive in controlling antigen-specific T cell responses. Presently, MS-based proteomics is the only unbiased platform capable of large-scale investigation of the collection of HLA bound peptides. This technology drives the field of antigen discovery by immunopeptidomics and presents a powerful avenue for personalized immunotherapy, for example, against cancer.
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