Details

Autor(en) / Beteiligte

• Fu, Rongrong
• Xu, Jin
• Guo, Qingcheng
• Liu, Tao
• Su, Xinyi
• Xu, Mengjiao
• Zhao, Xiang
• Wang, Fugui
• Ji, Lusha
• Qian, Weizhu
• Hou, Sheng
• Li, Jun
• Zhang, Dapeng
• Guo, Huaizu

Titel

Highly drug/target-tolerant neutralizing antibody (NAb) assay development through target-based drug depletion and drug-based NAb extraction for an anti-EGFR therapeutic monoclonal antibody

Ist Teil von

• Journal of pharmaceutical and biomedical analysis, 2024-04, Vol.241, p.116006-116006, Article 116006

Ort / Verlag

England: Elsevier B.V

Erscheinungsjahr

2024

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The reduction of immunogenicity is fundamental for the development of biobetter Erbitux, given that the development of an immune response reduces treatment efficacy and may lead to potential side effects. One of the requirements for the clinical research of a Erbitux biobetter candidate (CMAB009) is to develop a neutralizing antibody (NAb) assay, and sufficient drug and target tolerance for the assay is necessary. Here, we describe the development of a competitive ligand binding (CLB) assay for CMAB009 with high drug and target tolerance through target-based drug depletion and drug-based NAb extraction, the integrated experimental strategy was implemented to simultaneously mitigate drug interference and enhance target tolerance. Following troubleshooting and optimization, the NAb assay was validated for clinical sample analysis with the sensitivity of 92 ng/mL, drug tolerance of 70 μg/mL and target tolerance of 798 ng/mL. The innovative drug depletion and NAb extraction achieved though the combination of drug and target beads would enable the development of reliable NAb assays for many other therapeutics that overcome drug and its target interference for more precise and sensitive NAb assessment. •NAb assay developed with sufficient drug and target tolerance for EGFR mAb.•The first reported high drug/target-tolerant CLB NAb assay for the clinical research of an anti EGFR antibody.•A streamlined optimization strategy that enhances CLB NAb assays, enabling better evaluation of immunogenicity for biobetter development.