Formulation Development for Antibody-Drug Conjugates

Ji, Junyan A.; Li, Jun; Wang, Y. John

doi:10.1007/978-3-319-13081-1_5

Cited by 5 publications

(6 citation statements)

References 72 publications

(60 reference statements)

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“…As uncharged vc-MMAE conjugation through sulfhydryl groups in the interchain-cysteine residues is known not to change the net charge of the ADCs, similar charge variant profiles were expected between the conjugated and the unconjugated mAb. However, overlay of icIEF vc-MMAE ADC's profiles, incubated at pH 9 during 0 to 48 hours, showed an important heterogeneity in the acidic region due to various negative charges of the ADC gained from both deamidation and succinimide hydrolysis of the thio-succinimide linker [80]. Concerning lysine-linked ADC, this type of chemistry eliminates basic sites in the proteins and changes ADCs pIs [81].…”

Section: Applicationsmentioning

confidence: 99%

“…The nature of the drug-linker, especially the charge that can be added to the ADC represents a major concern on the charge profile of the protein. For example, Ji et al described the characterization of thio-succinimide hydrolysis of monomethyl auristatin E (vc-MMAE) ADC using icIEF during the formulation development [80]. As uncharged vc-MMAE conjugation through sulfhydryl groups in the interchain-cysteine residues is known not to change the net charge of the ADCs, similar charge variant profiles were expected between the conjugated and the unconjugated mAb.…”

Section: Applicationsmentioning

confidence: 99%

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Insights from capillary electrophoresis approaches for characterization of monoclonal antibodies and antibody drug conjugates in the period 2016–2018

Lechner

Giorgetti

Gahoual

et al. 2019

Journal of Chromatography B

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Monoclonal antibodies (mAbs) and their related products as antibody-drug-conjugates (ADCs) or biosimilars represent a constantly growing class of molecules therapeutic proteins used as treatment against numerous diseases. These compounds can undergo several modifications which could alter the efficiency of treatments. In this context, several analytical methods were designed to deliver a comprehensive structural characterization and guarantee the quality of biotherapeutics. Capillary electrophoresis (CE) is considered today as a major technique for the analysis of biotherapeutics due to benefic characteristics as high resolution separation and miniaturized format. Different CE modes have been developed to characterize mAbs at different levels such as capillary gel electrophoresis (CGE), capillary isoelectric focusing (cIEF), and capillary zone electrophoresis (CZE). Recent developments in CE-mass spectrometry (MS) coupling assessed this technology as a promising tool to obtain high level structural characterization of biopharmaceuticals. Moreover, upcoming techniques such as 2D CE-MS and microfluidic systems are now emerging to offer new possibilities beyond actual limits. This review will be dedicated to discuss the state-of-the-art CE-based methods for the characterization of mAbs and ADCs in the period 2016-2018.

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Section: Applicationsmentioning

confidence: 99%

Section: Applicationsmentioning

confidence: 99%

Insights from capillary electrophoresis approaches for characterization of monoclonal antibodies and antibody drug conjugates in the period 2016–2018

Lechner

Giorgetti

Gahoual

et al. 2019

Journal of Chromatography B

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“…Concerning ADCs, several cytotoxins have been conjugated to mAbs or their fragments through a variety of linkers. Together with the DAR and the drug load distribution, the stability of the linker are critical attributes for quality, safety, and efficacy of the therapeutic drug [132]. CIEF and iCIEF are among the techniques used for ADCs analysis.…”

Section: Goyon Et Al Used Icief To Analyze the Charge Variants And To...mentioning

confidence: 99%

Capillary electrophoresis of glycoproteins

Puerta

Gomez-Ruiz

Diez-Masa

et al. 2021

Carbohydrate Analysis by Modern Liquid Phase Separation Techniques

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“…The nature of the drug-linker, especially the charge that can or cannot be added to the ADC represents a major concern on the charge profile of the protein. For instance, Ji et al described the characterization of thio-succinimide hydrolysis of vc-MMAE ADC using icIEF during the formulation development[86]. As uncharged vc-MMAE conjugation through sulfhydryl groups in the interchain-cysteine residues is known not to change the net charge of the ADCs, similar charge variant profiles were expected between the conjugated and the unconjugated mAb.…”

mentioning

confidence: 99%

“…Each peak shift to the acidic region of the charge profiles represents a gain of one charge and then changes pI values. Based on this conclusion, an approach using weighted peak area and drug load has been utilized to quantify the thio-succinimide hydrolysis of ADCs[86].Adem et al described the same kind of results in the study of physical instability and the role of drug payload of vc-MMAE ADC [87]. They represented acidic variants variation of ADCs after formulation in either low and high ionic strength buffer and storage at 40°C for up to 4 weeks.…”

mentioning

confidence: 99%

Cutting-edge multi-level analytical and structural characterization of antibody-drug conjugates: present and future

Beck

D’Atri

Ehkirch

et al. 2019

Expert Review of Proteomics

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Introduction: The development and optimization of antibody drug conjugates (ADCs) rely on improving their analytical and bioanalytical characterization, by assessing critical quality attributes (CQAs). Among the CQAs, the glycoprofile, drug load distribution (DLD), the amount of unconjugated antibody (D0), the average drug-to-antibody ratio (DAR), the drug conjugation sites and the residual drug-linker and related product proportions (SMDs) in addition to high and low molecular weight species (H/LMWS) are the most important ones. Areas covered: The analytical and structural toolbox for the characterization of 1 st , 2 d and 3 d generation ADCs was significantly extended in the last 3 years. Here, we reviewed state-ofthe-art techniques, such as liquid chromatography, high resolution native and ion mobility mass spectrometry, multidimensional LC and capillary electrophoresis hyphenated to mass spectrometry, reported mainly since 2016. Expert commentary: These emerging techniques allow a deep insight into important CQAs that are related to ADC Chemistry Manufacturing and Control (CMC) as well as an improved understanding of in vitro and in vivo ADC biotransformations. This knowledge and the development of quantitative bioanalytical assays will continue to contribute to earlydevelopability assessment for the optimization of all the ADC components (i.e., antibody, drug, and linker) and help to bring next-generation candidate ADC into the clinic and hopefully to the market.

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Formulation Development for Antibody-Drug Conjugates

Cited by 5 publications

References 72 publications

Insights from capillary electrophoresis approaches for characterization of monoclonal antibodies and antibody drug conjugates in the period 2016–2018

Insights from capillary electrophoresis approaches for characterization of monoclonal antibodies and antibody drug conjugates in the period 2016–2018

Capillary electrophoresis of glycoproteins

Cutting-edge multi-level analytical and structural characterization of antibody-drug conjugates: present and future

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