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

  • ACS Omega. 2025 Aug 27;10(35):39912-39922. doi: 10.1021/acsomega.5c03733.
Duygu Erdogan  1  2 ,  Hulya Ayar Kayali  1  2  3
Affiliations
  • 1. Izmir International Biomedicine and Genome Institute, Dokuz Eylül University, Izmir 35340, Türkiye.
  • 2. Izmir Biomedicine and Genome Center, Izmir 35340, Türkiye.
  • 3. Department of Chemistry, Division of Biochemistry, Faculty of Science, Dokuz Eylül University, Izmir 35390, Türkiye.
PMID: 40949250 DOI: 10.1021/acsomega.5c03733
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.

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