Development of a Targeted Mass-Spectrometry Serum Assay To Quantify M-Protein in the Presence of Therapeutic Monoclonal Antibodies,Journal of Proteome Research

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Development of a Targeted Mass-Spectrometry Serum Assay To Quantify M-Protein in the Presence of Therapeutic Monoclonal Antibodies
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2018-02-15 00:00:00 , DOI: 10.1021/acs.jproteome.7b00890
Marina Zajec _{1,

2} , Joannes F. M. Jacobs ₃ , Patricia J. T. A. Groenen ₄ , Corrie M. de Kat Angelino ₃ , Christoph Stingl ₁ , Theo M. Luider ₁ , Yolanda B. De Rijke ₂ , Martijn M. VanDuijn ₁

Affiliation

M-protein diagnostics can be compromised for patients receiving therapeutic monoclonal antibodies as treatment in multiple myeloma. Conventional techniques are often not able to distinguish between M-proteins and therapeutic monoclonal antibodies administered to the patient. This may prevent correct response assessment and can lead to overtreatment. We have developed a serum-based targeted mass-spectrometry assay to detect M-proteins, even in the presence of three therapeutic monoclonal antibodies (daratumumab, ipilimumab, and nivolumab). This assay can target proteotypic M-protein peptides as well as unique peptides derived from therapeutic monoclonal antibodies. We address the sensitivity in M-protein diagnostics and show that our mass-spectrometry assay is more than two orders of magnitude more sensitive than conventional M-protein diagnostics. The use of stable isotope-labeled peptides allows absolute quantification of the M-protein and increases the potential of assay standardization across multiple laboratories. Finally, we discuss the position of mass-spectrometry assays in monitoring minimal residual disease in multiple myeloma, which is currently dominated by molecular techniques based on plasma cell assessment that requires invasive bone marrow aspirations or biopsies.

中文翻译：

在治疗性单克隆抗体存在下定量质谱血清的靶向质谱测定法的发展

对于多发性骨髓瘤中接受治疗性单克隆抗体治疗的患者，M蛋白诊断可能会受到影响。常规技术通常不能区分施用于患者的M蛋白和治疗性单克隆抗体。这可能会阻止正确的反应评估，并可能导致治疗过度。我们已经开发出一种基于血清的靶向质谱分析法，即使在三种治疗性单克隆抗体（daratumumab，ipilimumab和nivolumab）的存在下，也可以检测M蛋白。该测定法可以靶向蛋白型M蛋白肽以及源自治疗性单克隆抗体的独特肽。我们解决了M蛋白诊断中的敏感性问题，并表明我们的质谱测定法比常规M蛋白诊断的敏感性高出两个数量级。稳定同位素标记的肽的使用可对M蛋白进行绝对定量，并增加了跨多个实验室进行测定标准化的可能性。最后，我们讨论了质谱测定法在监测多发性骨髓瘤的最小残留病中的地位，目前该方法主要由基于需要侵入性骨髓穿刺或活检的浆细胞评估的分子技术所主导。

更新日期：2018-02-16

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