ArticleAntibodies (Basel, Switzerland)2023
Multiplex Bioanalytical Methods for Comprehensive Characterization and Quantification of the Unique Complementarity-Determining-Region Deamidation of MEDI7247, an Anti-ASCT2 Pyrrolobenzodiazepine Antibody-Drug Conjugate.
Article in Antibodies (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03106428 (A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies), which is not on this map. Cited by 6 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies
Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Review
- A novelmAbs · 2025Article
- Targets Selection for Precision Therapy of Relapsed/Refractory Multiple Myeloma: the Latest Advancements.Current treatment options in oncology · 2025Review
- Detailed Structural Elucidation of Antibody-Drug Conjugate Biotransformation Species Using High Resolution Multiple Reaction Monitoring Mass Spectrometry with Orthogonal Dissociation Methods.ACS pharmacology & translational science · 2025Article
- Development of a High-Throughput Platform for Quantitation of Histone Modifications on a New QTOF Instrument.Molecular & cellular proteomics : MCP · 2025Article
- Immunocapture mass spectrometry: macroscopic history, recent trends and future prospects.Bioanalysis · 2024Review
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Deamidation, a common post-translational modification, may impact multiple physiochemical properties of a therapeutic protein. MEDI7247, a pyrrolobenzodiazepine (PBD) antibody-drug conjugate (ADC), contains a unique deamidation site, N102, located within the complementarity-determining region (CDR), impacting the affinity of MEDI7247 to its target. Therefore, it was necessary to monitor MEDI7247 deamidation status in vivo. Due to the low dose, a sensitive absolute quantification method using immunocapture coupled with liquid chromatography-tandem mass spectrometry (LBA-LC-MS/MS) was developed and qualified. We characterized the isomerization via Electron-Activated Dissociation (EAD), revealing that deamidation resulted in iso-aspartic acid. The absolute quantification of deamidation requires careful assay optimization in order not to perturb the balance of the deamidated and nondeamidated forms. Moreover, the selection of capture reagents essential for the correct quantitative assessment of deamidation was evaluated. The final assay was qualified with 50 ng/mL LLOQ for ADC for total and nondeamidated antibody quantification, with qualitative monitoring of the deamidated antibody. The impact of deamidation on the pharmacokinetic characteristics of MEDI7247 from clinical trial NCT03106428 was analyzed, revealing a gradual reduction in the nondeamidated form of MEDI7247 in vivo. Careful quantitative biotransformation analyses of complex biotherapeutic conjugates help us understand changes in product PTMs after administration, thus providing a more complete view of in vivo pharmacology.
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