Mapping of the multiple myeloma cell surface N-glycoproteome and targeted validation
in patient samples uncovers immunotherapy targets
Oldham RAA, Faber ML, Keppel TR, Buchberger AR, Waas M, Hari P, Gundry RL, Medin JA. Discovery and validation of surface N-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets. J Immunother Cancer. 2020 Aug;8(2):e000915. doi: 10.1136/jitc-2020-000915. PMID: 32771993; PMCID: PMC7418848.
- Organism: Homo sapiens
- Instrument: Orbitrap Fusion Lumos
Cell Surface Capture, PRM, Multiple Myeloma
- Lab head:
Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow. While recent advances in treatment for MM have improved patient outcomes, the 5-year survival rate remains ~50%. A better understanding of the MM cell surface proteome could facilitate development of new therapies and assist in stratification and monitoring of patient outcomes. In this study, we used a mass spectrometry (MS)-based discovery approach termed cell surface capture (CSC) technology to map the cell surface N-glycoproteome of MM cell lines. We identified 696 MM cell surface N-glycoproteins by CSC and developed targeted detection assays for 73 proteins of interest. We then applied targeted MS analysis to primary MM patient samples, revealing 30 proteins with significantly higher abundance in patient MM cells than controls. Nine of these proteins were identified as potential immunotherapeutic targets, including five that are already under investigation for other cancers. These data will be a valuable resource in the development of biomarkers and therapeutics, and we anticipate that our targeted MS assays will have clinical benefit for the diagnosis, stratification, and treatment of MM patients.
Created on 2/5/20, 10:33 PM