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Novel approach that allows highly sensitive and specific identification of primary myeloma cell clones in blood with the potential of replacing standard immunofixation electrophoresis, avoid invasive and problematic bone marrow aspiration, and by that to facilitate early detection of disease relapse due to possibility of close patient monitoring at brief intervals.
Background:
• Multiple myeloma (MM) = cancer of plasma cells (PC) that produce monoclonal immunoglobulins (mAb, M-protein).
• Disease complications = high likelihood of developing persistent minimal residual disease (MRD) and relapse, both of which are associated with the presence of drug-resistant malignant plasma cell clone(s) - primary or emerged during treatment through clonal heterogeneity and evolution.
• Detection of minor and persistent clones from blood is currently limited = low sensitivity of current electrophoretic serum-based methods x more sensitive methods requiring invasive bone marrow biopsy.
• Main objective= to develop a simple and widely applicable method for sensitive detection of malignant PC clones based on antibodyanalysis in human serum. This method will allow early and sensitive detection of malignant clone progression.
Our Method:
• Isolation= selective affinity isolation of antibodies from a blood sample using ≤3 different affinity matrices.
• Analysis= separation and detection using conventional HPLC system with UV-VIS detector.
• Validation samples = 5 different mAb standards + 28 patient serum samples (pre and post treatment).
• Possible upgrade = automation of isolation procedure + sensitivity enhancement via mass spectrometric detection of clonotypic peptides.
Conclusion:
This novel approach allows highly sensitive and specific identification of primary myeloma cell clones in blood, those that become resistant and require following treatment as well as novel newly emerged clones. Additionally, the method enables distinguishing between pathological and therapeutic antibodies. The method employs a common analytical instrument, thus facilitating its widespread use. The method has a potential to replace standard immunofixation electrophoresis, avoid invasive and problematic bone marrow aspiration, and by that to facilitate early detection of disease relapse due to possibility of close patient monitoring at brief intervals.
IPR Status:Know-how
Stage of Development: Proof-of-Concept
University Hospital Hradec Králové is now one of the largest medical facilities not only in Eastern Bohemia but also throughout the Czech Republic. It is a state-of-the-art facility spanning a wide range of medical fields and serves as a catchment center for approximately 1,000,000 inhabitants from all over the Czech Republic.
More than 41,000 patients are hospitalized every year at the hospital’s 39 workplaces, which include 24 departments and over 1370 beds, with approximately 715,000 outpatients treated annually. The most complex surgical procedures are performed and modern diagnostic and treatment technologies are used. This makes University Hospital Hradec Králové comparable with similar hospitals in Europe.
University Hospital is an important research and educational institution closely connected with the Faculty of Medicine in Hradec Králové.
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