Particles in Biopharmaceutical Formulations, Part 2: An Update on Analytical Techniques and Applications for Therapeutic Proteins, Viruses, Vaccines and Cells

Roesch, Alexandra; Zölls, Sarah; Stadler, Daniela; Helbig, Constanze; Wuchner, Klaus; Kersten, Gideon; Hawe, Andrea; Jiskoot, Wim; Menzen, Tim

doi:10.1016/j.xphs.2021.12.011

Cited by 26 publications

(4 citation statements)

References 259 publications

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“…The ND/TU ratio was found to have a lower value (∼0.7) in the HEK293 cell harvest and rise to ∼1.0 in the fractions LVV AC1 and LVV AC2 eluted from the affinity column (Figure S8). The former value can be imputed to sample matrix interference 59 or to the fact that LVVs have higher activity prior to chromatographic processing. The wash fraction presented a ND/TU ∼ 1.7, indicating the removal of non-transducing virus particles and other particles present in the feed (note: the cell culture fluid also contains extracellular vesicles secreted by the HEK293 cells, micelles formed by shear protectants, etc.).…”

Section: Sec Peak Samplementioning

confidence: 99%

Multiangle Light Scattering as a Lentivirus Purification Process Analytical Technology

Sripada,

Barbieri,

Shastry

et al. 2024

Anal. Chem.

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The limited biomolecular and functional stability of lentiviral vectors (LVVs) for cell therapy poses the need for analytical tools that can monitor their titers and activity throughout the various steps of expression and purification. In this study, we describe a rapid (25 min) and reproducible (coefficient of variance ∼0.5−2%) method that leverages size exclusion chromatography coupled with multiangle light scattering detection (SEC-MALS) to determine size, purity, and particle count of LVVs purified from bioreactor harvests. The SEC-MALS data were corroborated by orthogonal methods, namely, dynamic light scattering (DLS) and transmission electron microscopy. The method was also evaluated for robustness in the range of 2.78 × 10 5 −2.67 × 10 7 particles per sample. Notably, MALS-based particle counts correlated with the titer of infectious LVVs measured via transduction assays (R 2 = 0.77). Using a combination of SEC-MALS and DLS, we discerned the effects of purification parameters on LVV quality, such as the separation between heterogeneous LV, which can facilitate critical decision-making in the biomanufacturing of gene and cell therapies.

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Section: Sec Peak Samplementioning

confidence: 99%

Multiangle Light Scattering as a Lentivirus Purification Process Analytical Technology

Sripada,

Barbieri,

Shastry

et al. 2024

Anal. Chem.

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“… 114 In addition, the fact that subvisible and visible particles are rarely analyzed during discovery and candidate selection is in many cases limited by the lack of high-throughput analytical techniques which can cope with the very limited sample volumes during early stages of development. 115 , 116 …”

Section: Orthogonal Approaches For the Selection Of Drug-like Antibodiesmentioning

confidence: 99%

Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties

Svilenov

Arosio

Menzen³

et al. 2023

mAbs

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Antibody drugs should exhibit not only high-binding affinity for their target antigens but also favorable physicochemical drug-like properties. Such drug-like biophysical properties are essential for the successful development of antibody drug products. The traditional approaches used in antibody drug development require significant experimentation to produce, optimize, and characterize many candidates. Therefore, it is attractive to integrate new methods that can optimize the process of selecting antibodies with both desired target-binding and drug-like biophysical properties. Here, we summarize a selection of techniques that can complement the conventional toolbox used to de-risk antibody drug development. These techniques can be integrated at different stages of the antibody development process to reduce the frequency of physicochemical liabilities in antibody libraries during initial discovery and to co-optimize multiple antibody features during early-stage antibody engineering and affinity maturation. Moreover, we highlight biophysical and computational approaches that can be used to predict physical degradation pathways relevant for long-term storage and in-use stability to reduce the need for extensive experimentation.

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“…The applications of viral vectors and nanomaterials are not limited to single treatment modes. They could be used in combination therapies, such as simultaneously delivering chemotherapy drugs and gene therapy [179]. For example, adeno-associated viruses enveloped within extracellular vesicles can facilitate improved delivery of therapeutic genes to the heart [180].…”

Section: Advantages Of Combinationmentioning

confidence: 99%

Joining Forces: The Combined Application of Therapeutic Viruses and Nanomaterials in Cancer Therapy

Li,

Zhu,

Wang

et al. 2023

Molecules

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Cancer, on a global scale, presents a monumental challenge to our healthcare systems, posing a significant threat to human health. Despite the considerable progress we have made in the diagnosis and treatment of cancer, realizing precision cancer therapy, reducing side effects, and enhancing efficacy remain daunting tasks. Fortunately, the emergence of therapeutic viruses and nanomaterials provides new possibilities for tackling these issues. Therapeutic viruses possess the ability to accurately locate and attack tumor cells, while nanomaterials serve as efficient drug carriers, delivering medication precisely to tumor tissues. The synergy of these two elements has led to a novel approach to cancer treatment—the combination of therapeutic viruses and nanomaterials. This advantageous combination has overcome the limitations associated with the side effects of oncolytic viruses and the insufficient tumoricidal capacity of nanomedicines, enabling the oncolytic viruses to more effectively breach the tumor’s immune barrier. It focuses on the lesion site and even allows for real-time monitoring of the distribution of therapeutic viruses and drug release, achieving a synergistic effect. This article comprehensively explores the application of therapeutic viruses and nanomaterials in tumor treatment, dissecting their working mechanisms, and integrating the latest scientific advancements to predict future development trends. This approach, which combines viral therapy with the application of nanomaterials, represents an innovative and more effective treatment strategy, offering new perspectives in the field of tumor therapy.

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Particles in Biopharmaceutical Formulations, Part 2: An Update on Analytical Techniques and Applications for Therapeutic Proteins, Viruses, Vaccines and Cells

Cited by 26 publications

References 259 publications

Multiangle Light Scattering as a Lentivirus Purification Process Analytical Technology

Multiangle Light Scattering as a Lentivirus Purification Process Analytical Technology

Approaches to expand the conventional toolbox for discovery and selection of antibodies with drug-like physicochemical properties

Joining Forces: The Combined Application of Therapeutic Viruses and Nanomaterials in Cancer Therapy

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