Antibody selection for antibody-drug conjugates (ADCs) has traditionally depended on its internalization into the target cell, although ADC efficacy also relies on recycling of the receptor-ADC complex, endo-lysosomal trafficking, and subsequent linker/antibody proteolysis. In this study, we observed that a bispecific anti-murine platelet-derived growth factor receptor beta (mPDGFRβ) x cotinine single-chain variable fragment (scFv)-kappa constant region (Cκ)-scFv fusion protein and cotinine-duocarmycin can form an ADC-like complex to induce cytotoxicity against mPDGFRβ expressing cells. Multiple anti-mPDGFRβ antibody candidates can be produced in this bispecific scFv-Cκ-scFv fusion protein format and tested for their ability to deliver cotinine-conjugated cytotoxic drugs, thus providing an improved approach for antibody selection in ADC development.

中文翻译：

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双特异性抗 mPDGFRβ x 可替宁 scFv-Cκ-scFv 融合蛋白和可替宁-duocarmycin 可形成抗体-药物偶联物样复合物，对 mPDGFRβ 表达细胞发挥细胞毒性

抗体-药物偶联物 (ADC) 的抗体选择传统上取决于其对靶细胞的内化，尽管 ADC 功效还依赖于受体-ADC 复合物的再循环、内溶酶体运输和随后的接头/抗体蛋白水解。在本研究中，我们观察到双特异性抗鼠血小板衍生生长因子受体β（mPDGFRβ）x可替宁单链可变片段（scFv）-κ恒定区（Cκ）-scFv融合蛋白与可替宁-杜卡霉素可形成ADC 样复合物诱导对 mPDGFRβ 表达细胞的细胞毒性。可以在这种双特异性 scFv-Cκ-scFv 融合蛋白形式中生产多种抗 mPDGFRβ 抗体候选物，并测试它们递送可替宁偶联的细胞毒性药物的能力，