Chemical de-conjugation for investigating the stability of small molecule drugs in antibody-drug conjugates

Chen, Tao; Su, Dian; Gruenhagen, Jason; Gu, Christine; Li, Yongguang; Yehl, Peter; Chetwyn, Nik P.; Medley, Colin D.

doi:10.1016/j.jpba.2015.09.015

Cited by 24 publications

(12 citation statements)

References 25 publications

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“…In addition to reduced ADC sample, RPLC can also be applied on the native ADC to separate L, H, HH, HL and HHL fragments (sub-units). This approach can be useful, as a second dimension separation of a HICxRPLC setup, prior to MS. On the other hand, RPLC can also be a useful tool to determine free drug residues, residual solvents or other preservatives of ADC formulations [36][37][38][39][40]. It is also often applied in comparability studies and stability testing, as a primary QC method.…”

Section: Reversed Phase Liquid Chromatographymentioning

confidence: 99%

Current possibilities of liquid chromatography for the characterization of antibody-drug conjugates

Bobály

Fleury-Souverain²,

Beck

et al. 2018

Journal of Pharmaceutical and Biomedical Analysis

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Antibody Drug Conjugates (ADCs) are innovative biopharmaceuticals gaining increasing attention over the last two decades. The concept of ADCs lead to new therapy approaches in numerous oncological indications as well in infectious diseases. Currently, around 60 CECs are in clinical trials indicating the expanding importance of this class of protein therapeutics. ADCs show unprecedented intrinsic heterogeneity and address new quality attributes which have to be assessed. Liquid chromatography is one of the most frequently used analytical method for the characterization of ADCs. This review summarizes recent results in the chromatographic characterization of ADCs and supposed to provide a general overview on the possibilities and limitations of current approaches for the evaluation of drug load distribution, determination of average drug to antibody ratio (DAR), and for the analysis of process/storage related impurities. Hydrophobic interaction chromatography (HIC), reversed phase liquid chromatography (RPLC), size exclusion chromatography (SEC) and multidimensional separations are discussed focusing on the analysis of marketed ADCs. Fundamentals and aspects of method development are illustrated with applications for each technique. Future perspectives in hydrophilic interaction chromatography (HILIC), HIC, SEC and ion exchange chromatography (IEX) are also discussed.

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Section: Reversed Phase Liquid Chromatographymentioning

confidence: 99%

Current possibilities of liquid chromatography for the characterization of antibody-drug conjugates

Bobály

Fleury-Souverain²,

Beck

et al. 2018

Journal of Pharmaceutical and Biomedical Analysis

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“…An example is the light-sensitivity in a model ADC using trastuzumab whereas trastuzumab itself does not show such sensitivity [179]. While much is known in the literature regarding the chemical stability of monoclonal antibodies [180] and the data on commonly used cytotoxic linker-payloads is accumulating [153,181,182], novel and non-toxic linker-payloads including siRNA will require a clear understanding of their degradation pathways in order to form control strategies during drug development process, similar to what has been demonstrated on payload metabolism [183]. Therefore, a comprehensive evaluation of the combined system will always be necessary for novel ADCs.…”

Section: Conjugate Developability Formulations and Characteristicsmentioning

confidence: 99%

Monoclonal Antibody-Directed Therapy

2022

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“…[10] A suitable response, particularly inflammation, is a critical parameter for the integration of implants and bone regeneration. [151] Excessive inflammation involving the M1 macrophage phenotype indeed promotes the release of proinflammatory cytokines and bone catabolic factors, which induce bone destruction and fibrous encapsulation, while M2 macrophage polarization (anti-inflammation) enhances the osteogenic differentiation of bone marrow stem cells (BMSCs). [152] Osteoimmunomodulation is currently considered an optimal strategy to facilitate the integration of bone biomaterials, and to improve their osteoinduction ability.…”

Section: Bone Biomaterialsmentioning

confidence: 99%

Immune Response to Silk Sericin–Fibroin Composites: Potential Immunogenic Elements and Alternatives for Immunomodulation

Boni

Bakadia

Osi

et al. 2021

Macromolecular Bioscience

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The unique properties of silk proteins (SPs), particularly silk sericin (SS) and silk fibroin (SF), have attracted attention in the design of scaffolds for tissue engineering over the past decades. Since SF has good mechanical properties, while SS displays bioactivity, scaffolds combining both proteins should exhibit complementary properties enhancing the potential of these materials. Unfortunately, SS-SF composites can generate chronic immune responses and their immunogenic element is not completely clear. The potential of SS-SF composites in tissue engineering, elements which may contribute to their immunogenicity, and alternatives for their preparation and design, to modulate the immune response and take advantage of their useful properties, are discussed in this review. It is known that SS can enhance 𝜷-sheet formation in SF, which may act as hydrophobic regions with a strong affinity for adsorption proteins inducing the chronic recruitment of inflammatory cells. Therefore, tailoring the exposure of hydrophobic regions at the scaffold surface should represent a viable strategy to modulate the immune response. This can be achieved by coating SS-SF composites with SS or other hydrophilic polymers, to take advantage of their antibiofouling properties. Research is still needed to realize the full potential of these composites for tissue engineering.

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Chemical de-conjugation for investigating the stability of small molecule drugs in antibody-drug conjugates

Cited by 24 publications

References 25 publications

Current possibilities of liquid chromatography for the characterization of antibody-drug conjugates

Current possibilities of liquid chromatography for the characterization of antibody-drug conjugates

Monoclonal Antibody-Directed Therapy

Immune Response to Silk Sericin–Fibroin Composites: Potential Immunogenic Elements and Alternatives for Immunomodulation

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