The characterization of cysteine-linked antibody‒drug conjugates (ADCs) can be more challenging than that of monoclonal antibodies (mAbs) and lysine-linked ADCs because the interchain disulfide bonds are reduced for payload conjugation, and the chains are noncovalently bonded to each other. Furthermore, payload conjugation and disulfide bond reduction/scrambling may introduce additional charge heterogeneity to biomolecules. This study illustrates an innovative workflow employing multiple separation techniques and tandem high-resolution mass spectrometry for comprehensive and in-depth characterization of disitamab vedotin, a recent-generation cysteine-linked ADC, including reversed-phase liquid chromatography (RPLC), ion exchange chromatography (IEX) and image capillary isoelectric focusing (icIEF). RPLC was employed for reduced chains analysis, subunit analysis and peptide mapping. IEX and icIEF were used for charge heterogeneity analysis. The innovation of the integrated methodology emphasizes the importance of cutting-edge icIEF-MS online coupling under near-native conditions to reveal the heterogeneity of disitamab vedotin.
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http://dx.doi.org/10.1016/j.chroma.2024.465353 | DOI Listing |
Front Oncol
December 2024
Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Objective: To explore the efficacy of c in the multiline treatment of late-stage lung adenocarcinoma with Her-2 overexpression and epidermal growth factor receptor (EGFR) mutations.
Methods: We summarize the diagnosis and treatment of a female patient with EGFR 21L858R mutation combined with Her-2 overexpression in advanced lung adenocarcinoma, and analyze the effect of c in her treatment process.
Results: The patient was diagnosed with lung adenocarcinoma 8 years ago.
Ann Oncol
December 2024
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital, Beijing, China. Electronic address:
Background: HER2-targeted antibody-drug conjugates (ADCs) such as disitamab vedotin (DV) and trastuzumab deruxtecan (T-Dxd) have emerged as effective treatment options and received regulatory approvals for HER2 expressing locally advanced or metastatic urothelial carcinoma (la/mUC). In addition, ADCs in combination with immunotherapy have demonstrated anti-tumor activity. The current study aimed to evaluate the combination of DV and toripalimab in patients with la/mUC.
View Article and Find Full Text PDFFront Oncol
November 2024
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Oncol
November 2024
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Oncologist
November 2024
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210009, People's Republic of China.
Background: Disitamab vedotin (RC48-ADC), an antibody-drug conjugate (ADC), combines specific antibody disitamab with cytotoxicity monomethyl auristatin E to effectively target the human epidermal growth factor receptor 2 (HER2) protein on tumor cells for precise elimination. Recent studies have demonstrated that RC48-ADC offers therapeutic benefits for patients with HER2-positive and HER2-low-expression breast cancer (BC). However, a thorough exploration of its efficacy and safety in real-world settings for patients with metastatic breast cancer (mBC) is currently lacking.
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