Antibodies to watch in 2022

Kaplon, Hélène; Chenoweth, Alicia; Crescioli, Silvia; Reichert, Janice M.

doi:10.1080/19420862.2021.2014296

Cited by 248 publications

(128 citation statements)

References 66 publications

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“…Antibodies belong to the most important biochemical reagents available today to detect, localize, identify and characterize biomolecules as well as their expression and functional status. In addition, therapeutic antibodies and antibody-drug conjugates are extremely valuable for the treatment of severe diseases, such as cancer and infections [ 1 , 2 , 3 , 4 ]. In all cases, the unambiguous definition and identification of such reagents or pharmaceuticals are of utmost relevance [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

MALDI-TOF-MS-Based Identification of Monoclonal Murine Anti-SARS-CoV-2 Antibodies within One Hour

et al. 2022

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During the SARS-CoV-2 pandemic, many virus-binding monoclonal antibodies have been developed for clinical and diagnostic purposes. This underlines the importance of antibodies as universal bioanalytical reagents. However, little attention is given to the reproducibility crisis that scientific studies are still facing to date. In a recent study, not even half of all research antibodies mentioned in publications could be identified at all. This should spark more efforts in the search for practical solutions for the traceability of antibodies. For this purpose, we used 35 monoclonal antibodies against SARS-CoV-2 to demonstrate how sequence-independent antibody identification can be achieved by simple means applied to the protein. First, we examined the intact and light chain masses of the antibodies relative to the reference material NIST-mAb 8671. Already half of the antibodies could be identified based solely on these two parameters. In addition, we developed two complementary peptide mass fingerprinting methods with MALDI-TOF-MS that can be performed in 60 min and had a combined sequence coverage of over 80%. One method is based on the partial acidic hydrolysis of the protein by 5 mM of sulfuric acid at 99 °C. Furthermore, we established a fast way for a tryptic digest without an alkylation step. We were able to show that the distinction of clones is possible simply by a brief visual comparison of the mass spectra. In this work, two clones originating from the same immunization gave the same fingerprints. Later, a hybridoma sequencing confirmed the sequence identity of these sister clones. In order to automate the spectral comparison for larger libraries of antibodies, we developed the online software ABID 2.0. This open-source software determines the number of matching peptides in the fingerprint spectra. We propose that publications and other documents critically relying on monoclonal antibodies with unknown amino acid sequences should include at least one antibody fingerprint. By fingerprinting an antibody in question, its identity can be confirmed by comparison with a library spectrum at any time and context.

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Section: Introductionmentioning

confidence: 99%

MALDI-TOF-MS-Based Identification of Monoclonal Murine Anti-SARS-CoV-2 Antibodies within One Hour

et al. 2022

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“…3 Different mAbs have been intensively researched for an effective treatment for COVID-19 patients. 4–6 Several mAb products, including anti-SARS-CoV-2 antibodies casirivimab + imdevimab (Ronaprev), 7 bamlanivimab + etesevimab, 8 sotrovimab (Xevudy®), 9 bebtelovimab, 10 regdanvimab (Regkirona), tixagevimab + cilgavimab (Evusheld), and amubarvimab + romlusevimab, 11 were developed at pandemic speed and they are either approved for emergency use or marketing applications are under consideration by numerous regulatory agencies. Many more mAbs for COVID-19 are under development at different clinical stages.…”

Section: Introductionmentioning

confidence: 99%

Upstream cell culture process characterization and in-process control strategy development at pandemic speed

McHugh

et al. 2022

mAbs

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As of early 2022, the coronavirus disease 2019 (COVID-19) pandemic remains a substantial global health concern. Different treatments for COVID-19, such as anti-COVID-19 neutralizing monoclonal antibodies (mAbs), have been developed under tight timelines. Not only mAb product and clinical development but also chemistry, manufacturing, and controls (CMC) process development at pandemic speed are required to address this highly unmet patient need. CMC development consists of early- and late-stage process development to ensure sufficient mAb manufacturing yield and consistent product quality for patient safety and efficacy. Here, we report a case study of late-stage cell culture process development at pandemic speed for mAb1 and mAb2 production as a combination therapy for a highly unmet patient treatment. We completed late-stage cell culture process characterization (PC) within approximately 4 months from the cell culture process definition to the initiation of the manufacturing process performance qualification (PPQ) campaign for mAb1 and mAb2, in comparison to a standard one-year PC timeline. Different strategies were presented in detail at different PC steps, i.e., pre-PC risk assessment, scale-down model development and qualification, formal PC experiments, and in-process control strategy development for a successful PPQ campaign that did not sacrifice quality. The strategies we present may be applied to accelerate late-stage process development for other biologics to reduce timelines.

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“…Advances in biologics production have improved access to treatments for complex diseases, including cancer, autoimmune diseases, and infectious diseases (Kaplon et al, 2022). Recently, the emergence of SARS‐CoV‐2 demonstrated the role of biologics production as critical infrastructure to rapidly respond to emerging diseases at scale (Kelley, 2020).…”

Section: Introductionmentioning

confidence: 99%

Engineering redox sensors into CHO cells enables near‐real‐time quantification of intracellular redox in bioprocesses

McFarland

Zhu

Sinharoy

et al. 2022

Biotech & Bioengineering

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The production of biologics that treat complex diseases, such as cancer, autoimmune, and infectious disease, requires careful monitoring and control of cell cultures. While bioprocess optimizations have dramatically improved production yields, a lack of analytical tools has made it challenging to identify accompanying intracellular improvements. Intracellular redox can diminish the growth and productivity of biologics-producing cells and adversely impact product quality profiles yet characterizing redox is challenging due to its complex and highly transient nature. In this study, we integrated a fluorescent thiol-based redox biosensor to monitor intracellular redox in one bisAb-and two monoclonal antibody-producing clonal cell lines in a 14-day fed-batch bioreactor. We characterized biosensor functionality using three fluorescence measurement techniques and determined sensor oxidation correlates with the intracellular ratio of reduced (GSH) and oxidized glutathione (GSSG), an important cellular antioxidant. Our fed-batch bioreactor studies showed that sensor expression minimally affected bioprocess outcomes, including growth, productivity, product quality attributes, or intracellular redox attributes, including mitochondrial reactive oxygen species and total cellular GSH levels in all cell lines tested. Biosensor measurements taken throughout the culture revealed that the intracellular environment in these cell lines became more reduced throughout the culture, with the exception of a high pH condition which became more oxidized. Our results demonstrate the potential of using biosensors to monitor intracellular changes in near-real-time with minimal process effects, thus potentially improving future bioprocess optimizations.

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Antibodies to watch in 2022

Cited by 248 publications

References 66 publications

MALDI-TOF-MS-Based Identification of Monoclonal Murine Anti-SARS-CoV-2 Antibodies within One Hour

MALDI-TOF-MS-Based Identification of Monoclonal Murine Anti-SARS-CoV-2 Antibodies within One Hour

Upstream cell culture process characterization and in-process control strategy development at pandemic speed

Engineering redox sensors into CHO cells enables near‐real‐time quantification of intracellular redox in bioprocesses

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