Suppr超能文献

合成的雷莫西尤单抗-维生素C-单甲基澳瑞他汀E作为卵巢癌潜在治疗方法的特性分析

Characterization of Synthesized Ramucirumab-vcMMAE as a Potential Therapeutic Approach in Ovarian Cancer.

作者信息

Erdogan Duygu, Ayar Kayali Hulya

机构信息

Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir 35340, Türkiye.

Izmir Biomedicine and Genome Center, Izmir 35340, Türkiye.

出版信息

ACS Omega. 2025 Aug 27;10(35):39912-39922. doi: 10.1021/acsomega.5c03733. eCollection 2025 Sep 9.

Abstract

Current chemotherapy for ovarian cancer, often detected at a late stage, causes side effects and drug resistance. This highlights the necessity for targeted drug delivery systems. The study focuses on in vitro testing of Antibody-Drug Conjugate (ADC) for smarter, more selective cancer cell targeting. In the study, the conjugate was synthesized by reducing the interchain disulfide bonds of Ramucirumab, followed by alkylation with mc-vc-PAB-MMAE (vcMMAE). The synthesized conjugate underwent structural, physicochemical, and functional analyses, followed by an assessment of its in vitro efficacy in ovarian cancer cell lines with normal, primary and metastatic characteristics. It was found that Ramucirumab-mc-vc-PAB-MMAE (R-vcMMAE) had a mean drug-to-antibody ratio of 3.2 and a monomeric protein content of over 95%. Moreover, the conjugation process had a low effect on the binding ability of R-vcMMAE to ovarian cancer cells. The results showed that the R-vcMMAE conjugate inhibited 50% of ovarian cancer cell viability at approximately 6 nM without affecting normal ovarian cell viability. In vitro studies indicated that the synthesized ADC exhibited minimal aggregation, did not adversely affect the antibody's binding to the antigen, and displayed efficacy.

摘要

卵巢癌通常在晚期才被发现,当前的化疗会产生副作用并导致耐药性。这凸显了靶向给药系统的必要性。该研究聚焦于抗体药物偶联物(ADC)的体外测试,以实现更智能、更具选择性的癌细胞靶向。在这项研究中,通过还原雷莫西尤单抗的链间二硫键,然后用mc-vc-PAB-MMAE(vcMMAE)进行烷基化反应来合成偶联物。对合成的偶联物进行了结构、物理化学和功能分析,随后评估其在具有正常、原发性和转移性特征的卵巢癌细胞系中的体外疗效。研究发现,雷莫西尤单抗-mc-vc-PAB-MMAE(R-vcMMAE)的平均药物与抗体比率为3.2,单体蛋白含量超过95%。此外,偶联过程对R-vcMMAE与卵巢癌细胞的结合能力影响较小。结果表明,R-vcMMAE偶联物在约6 nM时可抑制50%的卵巢癌细胞活力,而不影响正常卵巢细胞活力。体外研究表明,合成的ADC表现出最小程度的聚集,不会对抗体与抗原的结合产生不利影响,并显示出疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/baf4/12423901/b16235ac5207/ao5c03733_0001.jpg

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验