Determination of the Serum Concentrations of the Monoclonal Antibodies Bevacizumab, Rituximab, and Panitumumab Using Porous Membranes Containing Immobilized Peptide Mimotopes

Determination of the Serum Concentrations of the Monoclonal Antibodies Bevacizumab, Rituximab, and Panitumumab Using Porous Membranes Containing Immobilized Peptide Mimotopes
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DOI:
10.1021/acs.analchem.0c04903
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发表时间:
2021-05-17
影响因子:
7.4
通讯作者:
Bruening,Merlin L.
Bruening,Merlin L.
中科院分区:
化学1区
文献类型:
--
作者:
Berwanger,Joshua D.;Tan,Hui Yin;Bruening,Merlin L.

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有效的单克隆抗体 (mAb) 疗法需要患者血清中的 mAb 浓度达到阈值。此外,单克隆抗体贝伐珠单抗的血清浓度应处于特定范围内,以避免副作用。方便地测定患者血清中单克隆抗体水平的方法可以实现个性化剂量计划,从而实现更成功的治疗。这项工作利用用抗体结合肽功能化的微孔尼龙膜从稀释的 (25%) 血清中捕获贝伐单抗、利妥昔单抗或帕尼单抗。捕获肽末端的修饰对于产生有效结合所需的亲和力通常至关重要。洗脱的 mAb 纯度高,可以使用天然荧光进行定量,并且膜在任何实验室均可使用的旋转装置中非常有效。该技术在贝伐单抗浓度的治疗范围内有效。未来的工作旨在进一步修改以开发快速护理点设备并降低检测限。
Effective monoclonal antibody (mAb) therapies require a threshold mAb concentration in patient serum. Moreover, the serum concentration of the mAb Bevacizumab should reside in a specific range to avoid side effects. Methods for conveniently determining the levels of mAbs in patient sera could allow for personalized dosage schedules that lead to more successful treatments. This work utilizes microporous nylon membranes functionalized with antibody-binding peptides to capture Bevacizumab, Rituximab, or Panitumumab from diluted (25%) serum. Modification of the capture-peptide terminus is often crucial to creating the affinity necessary for effective binding. The high purity of eluted mAbs allows for their quantitation using native fluorescence, and membranes are effective in spin devices that can be used in any laboratory. The technique is effective over the therapeutic range of Bevacizumab concentrations. Future work aims at further modifications to develop rapid point-of-care devices and decrease detection limits.