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Evaluation of the impact of antibody fragments on aggregation of intact molecules via size exclusion chromatography coupled with native mass spectrometry mAbs (IF 5.3) Pub Date : 2024-03-27 Jing Xu, John E. Coughlin, Malgorzata Szyjka, Serene Jabary, Sonal Saluja, Zoran Sosic, Yunqiu Chen, Chong-Feng Xu
Aggregates are recognized as one of the most critical product-related impurities in monoclonal antibody (mAb)-based therapeutics due to their negative impact on the stability and safety of the drug...
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RUBY® – a tetravalent (2+2) bispecific antibody format with excellent functionality and IgG-like stability, pharmacology and developability properties mAbs (IF 5.3) Pub Date : 2024-03-25 Barnabas Nyesiga, Mattias Levin, Anna Säll, Anna Rosén, Kim Jansson, Sara Fritzell, Karin Hägerbrand, Dietmar Weilguny, Laura von Schantz
Despite the large number of existing bispecific antibody (bsAb) formats, the generation of novel bsAbs is still associated with development and bioprocessing challenges. Here, we present RUBY, a no...
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T and B cell epitope analysis for the immunogenicity evaluation and mitigation of antibody-based therapeutics mAbs (IF 5.3) Pub Date : 2024-03-21 Ruoxuan Sun, Mark G. Qian, Xiaobin Zhang
The surge in the clinical use of therapeutic antibodies has reshaped the landscape of pharmaceutical therapy for many diseases, including rare and challenging conditions. However, the administratio...
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Antibody-epitope conjugates deliver immunogenic T-cell epitopes more efficiently when close to cell surfaces mAbs (IF 5.3) Pub Date : 2024-03-18 W. van der Wulp, W. Luu, M. E. Ressing, J. Schuurman, S. I. van Kasteren, L. Guelen, R. C. Hoeben, B. Bleijlevens, M. H. M. Heemskerk
Antibody-mediated delivery of immunogenic viral CD8+ T-cell epitopes to redirect virus-specific T cells toward cancer cells is a promising new therapeutic avenue to increase the immunogenicity of t...
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Reduction of monoclonal antibody viscosity using interpretable machine learning mAbs (IF 5.3) Pub Date : 2024-03-12 Emily K. Makowski, Hsin-Ting Chen, Tiexin Wang, Lina Wu, Jie Huang, Marissa Mock, Patrick Underhill, Emma Pelegri-O’Day, Erick Maglalang, Dwight Winters, Peter M. Tessier
Early identification of antibody candidates with drug-like properties is essential for simplifying the development of safe and effective antibody therapeutics. For subcutaneous administration, it i...
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Do antibody CDR loops change conformation upon binding? mAbs (IF 5.3) Pub Date : 2024-03-13 Chu’nan Liu, Lilian M. Denzler, Oliver E.C. Hood, Andrew C.R. Martin
Antibodies have increasingly been developed as drugs with over 100 now licensed in the US or EU. During development, it is often necessary to increase or reduce the affinity of an antibody and rati...
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A pivotal decade for bispecific antibodies? mAbs (IF 5.3) Pub Date : 2024-03-11 Marlena Surowka, Christian Klein
Bispecific antibodies (bsAbs) are a class of antibodies that can mediate novel mechanisms of action compared to monospecific monoclonal antibodies (mAbs). Since the discovery of mAbs and their adop...
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Exploring molecular determinants and pharmacokinetic properties of IgG1-scFv bispecific antibodies mAbs (IF 5.3) Pub Date : 2024-03-06 Kristina M.J. Aertker, Minu Ravindra Pilvankar, Tobias M. Prass, Michaela Blech, Fabian Higel, Srinath Kasturirangan
Bispecific antibodies (BsAbs) capable of recognizing two distinct epitopes or antigens offer promising therapeutic options for various diseases by targeting multiple pathways. The favorable pharmac...
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A novel conditional active biologic anti-EpCAM x anti-CD3 bispecific antibody with synergistic tumor selectivity for cancer immunotherapy mAbs (IF 5.3) Pub Date : 2024-03-06 Gerhard Frey, Ana Paula G. Cugnetti, Haizhen Liu, Charles Xing, Christina Wheeler, Hwai Wen Chang, William J. Boyle, Jay M. Short
Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein that plays several roles in cancer biology. EpCAM is an attractive therapeutic target because of its expression in most sol...
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Improving the integrity and reproducibility of research that uses antibodies: a technical, data sharing, behavioral and policy challenge mAbs (IF 5.3) Pub Date : 2024-03-06 M. Biddle, P. Stylianou, M. Rekas, A. Wright, J. Sousa, D. Ruddy, M. I. Stefana, K. Kmiecik, A. Bandrowski, R.A. Kahn, C. Laflamme, E. M. Krockow, H.S. Virk
Antibodies are one of the most important reagents used in biomedical and fundamental research, used to identify, and quantify proteins, contribute to knowledge of disease mechanisms, and validate d...
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Proceedings of the 14th European immunogenicity platform open symposium on immunogenicity of biopharmaceuticals mAbs (IF 5.3) Pub Date : 2024-03-05 Sophie Tourdot, Daniel Baltrunkonis, Sofie Denies, Viswanath Devanarayan, Joanna Grudzinska-Goebel, Arno Kromminga, Gregor P. Lotz, Laurent Malherbe, Lydia Michaut, Karin N. Weldingh, Joao A. Pedras-Vasconcelos, Laura. I. Salazar-Fontana, Sebastian Spindeldreher, Zuben Sauna, Veerle Snoeck, Daniela Verthelyi, Daniel Kramer
Biologics have revolutionized disease management in many therapeutic areas by addressing unmet medical needs and overcoming resistance to standard-of-care treatment in numerous patients. However, t...
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Biparatopic antibodies: therapeutic applications and prospects mAbs (IF 5.3) Pub Date : 2024-03-04 David L. Niquille, Kyle M. Fitzgerald, Nimish Gera
Biparatopic antibodies (bpAbs) bind distinct, non-overlapping epitopes on an antigen. This unique binding mode enables new mechanisms of action beyond monospecific and bispecific antibodies (bsAbs)...
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Application of quantitative protein mass spectrometric data in the early predictive analysis of membrane-bound target engagement by monoclonal antibodies mAbs (IF 5.3) Pub Date : 2024-03-04 Armin Sepp, Morris Muliaditan
Model-informed drug discovery advocates the use of mathematical modeling and simulation for improved efficacy in drug discovery. In the case of monoclonal antibodies (mAbs) against cell membrane an...
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Facilitating high throughput bispecific antibody production and potential applications within biopharmaceutical discovery workflows mAbs (IF 5.3) Pub Date : 2024-02-21 Caitlin Fawcett, Joseph. R. Tickle, Charlotte. H. Coles
A major driver for the recent investment surge in bispecific antibody (bsAb) platforms and products is the multitude of distinct mechanisms of action that bsAbs offer compared to a combination of t...
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Production of antibodies and antibody fragments containing non-natural amino acids in Escherichia coli mAbs (IF 5.3) Pub Date : 2024-02-21 Jacquelyn Blake-Hedges, Dan Groff, Wilson Foo, Jeffrey Hanson, Elenor Castillo, Miao Wen, Diana Cheung, Mary Rose Masikat, Jian Lu, Young Park, Nina Abi Carlos, Hans Usman, Kevin Fong, Abigail Yu, Sihong Zhou, Joyce Kwong, Cuong Tran, Xiaofan Li, Dawei Yuan, Trevor Hallam, Gang Yin
Therapeutic bioconjugates are emerging as an essential tool to combat human disease. Site-specific conjugation technologies are widely recognized as the optimal approach for producing homogeneous d...
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Impact of antibody architecture and paratope valency on effector functions of bispecific NKp30 x EGFR natural killer cell engagers mAbs (IF 5.3) Pub Date : 2024-02-19 Ammelie Svea Boje, Lukas Pekar, Katharina Koep, Britta Lipinski, Brian Rabinovich, Andreas Evers, Carina Lynn Gehlert, Steffen Krohn, Yanping Xiao, Simon Krah, Rinat Zaynagetdinov, Lars Toleikis, Sven Poetzsch, Matthias Peipp, Stefan Zielonka, Katja Klausz
Natural killer (NK) cells emerged as a promising effector population that can be harnessed for anti-tumor therapy. In this work, we constructed NK cell engagers (NKCEs) based on NKp30-targeting sin...
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Structure- and machine learning-guided engineering demonstrate that a non-canonical disulfide in an anti-PD-1 rabbit antibody does not impede antibody developability mAbs (IF 5.3) Pub Date : 2024-02-14 Wei-Ching Liang, Hongkang Xi, Dawei Sun, Luigi D’Ascenzo, Jonathan Zarzar, Nicole Stephens, Ryan Cook, Yinyin Li, Zhengmao Ye, Marissa Matsumoto, Jian Payandeh, Matthieu Masureel, Yan Wu
Rabbits produce robust antibody responses and have unique features in their antibody repertoire that make them an attractive alternative to rodents for in vivo discovery. However, the frequent occu...
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CC-96673 (BMS-986358), an affinity-tuned anti-CD47 and CD20 bispecific antibody with fully functional fc, selectively targets and depletes non-Hodgkin’s lymphoma mAbs (IF 5.3) Pub Date : 2024-02-13 Dan Zhu, Haralambos Hadjivassiliou, Catherine Jennings, David Mikolon, Massimo Ammirante, Sharmistha Acharya, Jon Lloyd, Mahan Abbasian, Rama Krishna Narla, Joseph R. Piccotti, Katie Stamp, Ho Cho, Kandasamy Hariharan
Cluster of differentiation 47 (CD47) is a transmembrane protein highly expressed in tumor cells that interacts with signal regulatory protein alpha (SIRPα) and triggers a “don’t eat me” signal to t...
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Electrostatic properties of human germlines and biodistribution of small biologics mAbs (IF 5.3) Pub Date : 2024-02-09 Leticia Maria De Souza Cordeiro, Kelley Christine Atkinson, Argin Aivazian, Patrick Frank Joyce, Fang Jia, Alessandro Mascioni
Off-target biodistribution of biologics bears important toxicological consequences. Antibody fragments intended for use as vectors of cytotoxic payloads (e.g. antibody-drug conjugates, radiotherapy...
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Charge heterogeneity of therapeutic monoclonal antibodies by different cIEF systems: views on the current situation mAbs (IF 5.3) Pub Date : 2024-02-08 Alessandro Ascione, Marcello Belfiore, Jaana Vesterinen, Mihaela Buda, Wolf Holtkamp, Francesca Luciani
Therapeutic mAbs show a specific “charge fingerprint” that may affect safety and efficacy, and, as such, it is often identified as a critical quality attribute (CQA). Capillary iso-electric focusin...
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In-situ biophysical characterization of high-concentration protein formulations using wNMR mAbs (IF 5.3) Pub Date : 2024-02-01 Jing Song, Marc Taraban, Y. Bruce Yu, Lynn Lu, Pallavi Guha Biswas, Wei Xu, Hanmi Xi, Akhilesh Bhambhani, Guangli Hu, Yongchao Su
High-concentration protein formulation is of paramount importance in patient-centric drug product development, but it also presents challenges due to the potential for enhanced aggregation and incr...
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Variable domain mutational analysis to probe the molecular mechanisms of high viscosity of an IgG1 antibody mAbs (IF 5.3) Pub Date : 2024-01-25 Jing Dai, Saeed Izadi, Jonathan Zarzar, Patrick Wu, Angela Oh, Paul J. Carter
Subcutaneous injection is the preferred route of administration for many antibody therapeutics for reasons that include its speed and convenience. However, the small volume limit (typically ≤2 mL) ...
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A tailored lectin microarray for rapid glycan profiling of therapeutic monoclonal antibodies mAbs (IF 5.3) Pub Date : 2024-01-22 Shen Luo, Baolin Zhang
Glycosylation plays a crucial role in determining the quality and efficacy of therapeutic antibodies. This necessitates a thorough analysis and monitoring process to ensure consistent product quali...
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Interactions of the anti-FcRn monoclonal antibody, rozanolixizumab, with Fcγ receptors and functional impact on immune cells in vitro mAbs (IF 5.3) Pub Date : 2024-01-19 Omar S. Qureshi, Emma J. Sutton, Rosemary F. Bithell, Shauna M. West, Rona M. Cutler, Gillian McCluskey, Graham Craggs, Asher Maroof, Nicholas M. Barnes, David P. Humphreys, Stephen Rapecki, Bryan J. Smith, Anthony Shock
Rozanolixizumab is a humanized anti-neonatal Fc receptor (FcRn) monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4) sub-class, currently in clinical development for the treatment of IgG autoa...
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Engineering hydrophobicity and manufacturability for optimized biparatopic antibody–drug conjugates targeting c-MET mAbs (IF 5.3) Pub Date : 2024-01-12 Andreas Evers, Simon Krah, Deniz Demir, Ramona Gaa, Desislava Elter, Christian Schroeter, Stefan Zielonka, Nicolas Rasche, Julia Dotterweich, Christine Knuehl, Achim Doerner
Optimal combinations of paratopes assembled into a biparatopic antibody have the capacity to mediate high-grade target cross-linking on cell membranes, leading to degradation of the target, as well...
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Antibodies to watch in 2024 mAbs (IF 5.3) Pub Date : 2024-01-05 Silvia Crescioli, Hélène Kaplon, Alicia Chenoweth, Lin Wang, Jyothsna Visweswaraiah, Janice M. Reichert
The ‘Antibodies to Watch’ article series provides an annual summary of commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and t...
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Therapeutic efficacy of a potent anti-Venezuelan equine encephalitis virus antibody is contingent on Fc effector function mAbs (IF 5.3) Pub Date : 2024-01-03 Jennifer L. Schwedler, Maxwell A. Stefan, Christine E. Thatcher, Peter R. McIlroy, Anupama Sinha, Ashlee M. Phillips, Christopher A. Sumner, Colleen M. Courtney, Christina Y. Kim, Dina R. Weilhammer, Brooke Harmon
The development of specific, safe, and potent monoclonal antibodies (Abs) has led to novel therapeutic options for infectious disease. In addition to preventing viral infection through neutralizati...
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Comprehensive characterization of higher order structure changes in methionine oxidized monoclonal antibodies via NMR chemometric analysis and biophysical approaches mAbs (IF 5.3) Pub Date : 2023-12-20 Mingyue Li, Victor A. Beaumont, Shahajahan Akbar, Hannah Duncan, Arch Creasy, Wenge Wang, Kelly Sackett, Lisa Marzilli, Jason C. Rouse, Hai-Young Kim
The higher order structure (HOS) of monoclonal antibodies (mAbs) is an important quality attribute with strong contribution to clinically relevant biological functions and drug safety. Due to the m...
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Determining the affinities of high-affinity antibodies using KinExA and surface plasmon resonance mAbs (IF 5.3) Pub Date : 2023-12-13 M. Frank Erasmus, Molly Dovner, Fortunato Ferrara, Sara D’Angelo, André A. Teixeira, Camila Leal-Lopes, Laura Spector, Elizabeth Hopkins, Andrew R. M. Bradbury
Accurate and efficient affinity measurement techniques are essential for the biophysical characterization of therapeutic monoclonal antibodies, one of the fastest growing drug classes. Surface plas...
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Accelerating the speed of innovative anti-tumor drugs to first-in-human trials incorporating key de-risk strategies mAbs (IF 5.3) Pub Date : 2023-12-14 Yuqi Wang, Quan Quan, Camille Gleason, Helin Yu, Lujia Peng, Yanshen Kang, Ling Jiang, Kailun Wu, Jie Pan, Moxiyele Bao, Qing Zhu, Meiqi Yi, Ming Fang, Yue Zheng, Ling Qiu, Bin Xu, Xiang Li, Jinfeng Song, Jiamu Sun, Zheng Zhang, Zijun Su, Jara Lin, Yuanyuan Xie, April Xu, Xiling Song, Chichi Huang, Zhirong Shen, Lai Wang, Jing Song
Pharmaceutical companies have recently focused on accelerating the timeline for initiating first-in-human (FIH) trials to allow quick assessment of biologic drugs. For example, a stable cell pool c...
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Discovery of ginisortamab, a potent and novel anti-gremlin-1 antibody in clinical development for the treatment of cancer mAbs (IF 5.3) Pub Date : 2023-12-12 Gareth C. G. Davies, Neesha Dedi, Paul S. Jones, Lara Kevorkian, David McMillan, Cristina Ottone, Monika-Sarah E. D. Schulze, Anthony Scott-Tucker, Roohi Tewari, Shauna West, Michael Wright, Tania F. Rowley
Gremlin-1, a high-affinity antagonist of bone morphogenetic proteins (BMP)-2, −4, and −7, is implicated in tumor initiation and progression. Increased gremlin-1 expression, and therefore suppressed...
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Breaking barriers in antibody discovery: harnessing divergent species for accessing difficult and conserved drug targets mAbs (IF 5.3) Pub Date : 2023-12-05 Soma S.R. Banik, Natasha Kushnir, Benjamin J. Doranz, Ross Chambers
To exploit highly conserved and difficult drug targets, including multipass membrane proteins, monoclonal antibody discovery efforts increasingly rely on the advantages offered by divergent species...
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Development and pharmacokinetic assessment of a fully canine anti-PD-1 monoclonal antibody for comparative translational research in dogs with spontaneous tumors mAbs (IF 5.3) Pub Date : 2023-12-04 Sho Yoshimoto, Nicholas Chester, Ailian Xiong, Enrico Radaelli, Hong Wang, Marc Brillantes, Gayathri Gulendran, Patrick Glassman, Don L. Siegel, Nicola J. Mason
PD-1 checkpoint inhibitors have revolutionized the treatment of patients with different cancer histologies including melanoma, renal cell carcinoma, and non-small cell lung carcinoma. However, only...
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Anti-citrullinated histone monoclonal antibody CIT-013, a dual action therapeutic for neutrophil extracellular trap-associated autoimmune diseases mAbs (IF 5.3) Pub Date : 2023-11-29 Maarten van der Linden, Sangeeta Kumari, Daphne Montizaan, Stephanie van Dalen, Annemarie Kip, Martyn Foster, Inge Reinieren-Beeren, Elsa Neubert, Luise Erpenbeck, Kelsy Waaijenberg, Tirza Bruurmijn, Rezie te Poele, Peter van Zandvoort, Paul Vink, Eric Meldrum, Helmuth van Es, Renato G.S. Chirivi
Neutrophil extracellular traps (NETs) contribute to the pathophysiology of multiple inflammatory and autoimmune diseases. Targeting the NETosis pathway has demonstrated significant therapeutic pote...
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Monoclonal antibody and protein therapeutic formulations for subcutaneous delivery: high-concentration, low-volume vs. low-concentration, high-volume mAbs (IF 5.3) Pub Date : 2023-11-27 M. Desai, A. Kundu, M. Hageman, H. Lou, D. Boisvert
Biologic drugs are used to treat a variety of cancers and chronic diseases. While most of these treatments are administered intravenously by trained healthcare professionals, a noticeable trend has...
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Epitope mapping of monoclonal antibodies: a comprehensive comparison of different technologies mAbs (IF 5.3) Pub Date : 2023-11-27 Xibei Dang, Lars Guelen, David Lutje Hulsik, Grigori Ermakov, Edward J. Hsieh, Joost Kreijtz, Judith Stammen-Vogelzangs, Imke Lodewijks, Astrid Bertens, Arne Bramer, Marco Guadagnoli, Alexis Nazabal, Andrea van Elsas, Thierry Fischmann, Veronica Juan, Amy Beebe, Maribel Beaumont, Hans van Eenennaam
Monoclonal antibodies have become an important class of therapeutics in the last 30 years. Because the mechanism of action of therapeutic antibodies is intimately linked to their binding epitopes, ...
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BERT2DAb: a pre-trained model for antibody representation based on amino acid sequences and 2D-structure mAbs (IF 5.3) Pub Date : 2023-11-27 Xiaowei Luo, Fan Tong, Wenbin Zhao, Xiangwen Zheng, Jiangyu Li, Jing Li, Dongsheng Zhao
Prior research has generated a vast amount of antibody sequences, which has allowed the pre-training of language models on amino acid sequences to improve the efficiency of antibody screening and o...
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Robust production of monovalent bispecific IgG antibodies through novel electrostatic steering mutations at the CH1-Cλ interface mAbs (IF 5.3) Pub Date : 2023-11-06 John D. Bagert, Vaheh Oganesyan, Chi-I Chiang, Mike Iannotti, Jia Lin, Chunning Yang, Sterling Payne, Will McMahon, Samuel Edwards, Andrew Dippel, Mark Hutchinson, Fengying Huang, Vineela Aleti, Chendi Niu, Chen Qian, Jessica Denham, Sofia Ferreira, Pallab Pradhan, Mark Penney, Chunlei Wang, Wenhai Liu, Even Walseng, Yariv Mazor
Bispecific antibodies represent an increasingly large fraction of biologics in therapeutic development due to their expanded scope in functional capabilities. Asymmetric monovalent bispecific IgGs ...
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A window into the human immune system: comprehensive characterization of the complexity of antibody complementary-determining regions in functional antibodies mAbs (IF 5.3) Pub Date : 2023-10-24 Oscar Mejias-Gomez, Andreas V. Madsen, Kerstin Skovgaard, Lasse E. Pedersen, J. Preben Morth, Timothy P. Jenkins, Peter Kristensen, Steffen Goletz
The human immune system uses antibodies to neutralize foreign antigens. They are composed of heavy and light chains, both with constant and variable regions. The variable region has six hypervariab...
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Delivery of the Brainshuttle™ amyloid-beta antibody fusion trontinemab to non-human primate brain and projected efficacious dose regimens in humans mAbs (IF 5.3) Pub Date : 2023-10-12 Hans Peter Grimm, Vanessa Schumacher, Martin Schäfer, Sabine Imhof-Jung, Per-Ola Freskgård, Kevin Brady, Carsten Hofmann, Petra Rüger, Tilman Schlothauer, Ulrich Göpfert, Maximilian Hartl, Sylvia Rottach, Adrian Zwick, Shanon Seger, Rachel Neff, Jens Niewoehner, Niels Janssen
There are few treatments that slow neurodegeneration in Alzheimer’s disease (AD), and while therapeutic antibodies are being investigated in clinical trials for AD treatment, their access to the ce...
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Utility of physiologically based pharmacokinetic modeling to predict inter-antibody variability in monoclonal antibody pharmacokinetics in mice mAbs (IF 5.3) Pub Date : 2023-10-12 Shufang Liu, Sara C. Humphreys, Kevin D. Cook, Kip P. Conner, Ana R. Correia, Alex W. Jacobitz, Melissa Yang, Ronya Primack, Marcus Soto, Rupa Padaki, Mariusz Lubomirski, Richard Smith, Marissa Mock, Veena A. Thomas
In this investigation, we tested the hypothesis that a physiologically based pharmacokinetic (PBPK) model incorporating measured in vitro metrics of off-target binding can largely explain the inter...
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A library approach for the de novo high-throughput isolation of humanized VHH domains with favorable developability properties following camelid immunization mAbs (IF 5.3) Pub Date : 2023-09-27 Paul Arras, Han Byul Yoo, Lukas Pekar, Christian Schröter, Thomas Clarke, Simon Krah, Daniel Klewinghaus, Vanessa Siegmund, Andreas Evers, Stefan Zielonka
In this study, we generated a novel library approach for high throughput de novo identification of humanized single-domain antibodies following camelid immunization. To achieve this, VHH-derived co...
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Identification of tyrosine sulfation in the variable region of a bispecific antibody and its effect on stability and biological activity mAbs (IF 5.3) Pub Date : 2023-09-24 Christopher B. Lietz, Ekaterina Deyanova, Younhee Cho, Jon Cordia, Sarah Franc, Sally Kabro, Steven Wang, David Mikolon, Douglas D. Banks
Despite tyrosine sulfation being a relatively common post-translational modification (PTM) on the secreted proteins of higher eukaryotic organisms, there have been surprisingly few reports of this ...
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Multivalent design of the monoclonal SynO2 antibody improves binding strength to soluble α-Synuclein aggregates mAbs (IF 5.3) Pub Date : 2023-09-22 Inga Petersen, Muhammad Ilyas Ali, Alex Petrovic, Anders Jimmy Ytterberg, Karin Staxäng, Monika Hodik, Fadi Rofo, Sina Bondza, Greta Hultqvist
Soluble aggregates are reported to be the most neurotoxic species of α-Synuclein (αSyn) in Parkinson’s disease (PD) and hence are a promising target for diagnosis and treatment of PD. However, the ...
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Discovery and characterization of prolactin neutralizing monoclonal antibodies for the treatment of female-prevalent pain disorders mAbs (IF 5.3) Pub Date : 2023-09-12 Stephanie Maciuba, Gregory D. Bowden, Harrison J. Stratton, Kazimierz Wisniewski, Claudio D. Schteingart, Juan C. Almagro, Philippe Valadon, Joshua Lowitz, Scott M. Glaser, Grace Lee, Mahdi Dolatyari, Edita Navratilova, Frank Porreca, Pierre J.M. Rivière
ABSTRACT Prolactin (PRL) has recently been demonstrated to elicit female-selective nociceptor sensitization and increase pain-like behaviors in female animals. Here we report the discovery and characterization of first-in-class, humanized PRL neutralizing monoclonal antibodies (PRL mAbs). We obtained two potent and selective PRL mAbs, PL 200,031 and PL 200,039. PL 200,031 was engineered as human IgG1
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Development of in silico models to predict viscosity and mouse clearance using a comprehensive analytical data set collected on 83 scaffold-consistent monoclonal antibodies mAbs (IF 5.3) Pub Date : 2023-09-12 Marissa Mock, Alex W. Jacobitz, Christopher James Langmead, Athena Sudom, Daniel Yoo, Sara C. Humphreys, Mai Alday, Larysa Alekseychyk, Nicolas Angell, Vivian Bi, Hannah Catterall, Chen-Chun Chen, Hui-Ting Chou, Kip P. Conner, Kevin D. Cook, Ana R. Correia, Andrew Dykstra, Sudipa Ghimire-Rijal, Kevin Graham, Peter Grandsard, Joon Huh, John O. Hui, Mani Jain, Victoria Jann, Lei Jia, Sheree Johnstone
ABSTRACT Biologic drug discovery pipelines are designed to deliver protein therapeutics that have exquisite functional potency and selectivity while also manifesting biophysical characteristics suitable for manufacturing, storage, and convenient administration to patients. The ability to use computational methods to predict biophysical properties from protein sequence, potentially in combination with
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Rapid in vitro assessment of the immunogenicity potential of engineered antibody therapeutics through detection of CD4+ T cell interleukin-2 secretion mAbs (IF 5.3) Pub Date : 2023-09-08 Yoshiyuki Arata, Shigeki Motoyama, Mariko Yano, Tatsuya Ikuno, Shunsuke Ito, Tomochika Matsushita, Akira Takeiri, Yukari Nishito, Nami Yabuki, Hideaki Mizuno, Zenjiro Sampei, Masayuki Mishima, Masaki Honda, Jumpei Kiyokawa, Hiromi Suzuki, Shuichi Chiba, Mitsuyasu Tabo, Chiyomi Kubo
ABSTRACT Therapeutic antibodies sometimes elicit anti-drug antibodies (ADAs) that can affect efficacy and safety. Engineered antibodies that contain artificial amino acid sequences are potentially highly immunogenic, but this is currently difficult to predict. Therefore, it is important to efficiently assess immunogenicity during the development of complex antibody-based formats. Here, we present an
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Biophysical characterization of PVR family interactions and therapeutic antibody recognition to TIGIT mAbs (IF 5.3) Pub Date : 2023-09-07 SJ J. Diong, Aarti Jashnani, Andrew W. Drake, Christine Bee, Felix Findeisen, Gavin Dollinger, Feng Wang, Arvind Rajpal, Pavel Strop, Peter S. Lee
ABSTRACT The clinical successes of immune checkpoint blockade have invigorated efforts to activate T cell-mediated responses against cancer. Targeting members of the PVR family, consisting of inhibitory receptors TIGIT, CD96, and CD112R, has been an active area of clinical investigation. In this study, the binding interactions and molecular assemblies of the PVR family receptors and ligands have been
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Mammalian display to secretion switchable libraries for antibody preselection and high throughput functional screening mAbs (IF 5.3) Pub Date : 2023-08-30 Ramona Gaa, Hannah Melina Mayer, Daniela Noack, Kavita Kumari, Ralf Guenther, Shang-Pu Tsai, Qingyong Ji, Achim Doerner
ABSTRACT Recently, there has been a co-evolution of mammalian libraries and diverse microfluidic approaches for therapeutic antibody hit discovery. Mammalian libraries enable the preservation of full immune repertoires, produce hit candidates in final format and facilitate broad combinatorial bispecific antibody screening, while several available microfluidic methodologies offer opportunities for rapid
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Exploration of the antibody–drug conjugate clinical landscape mAbs (IF 5.3) Pub Date : 2023-08-28 Heather Maecker, Vidya Jonnalagadda, Sunil Bhakta, Vasu Jammalamadaka, Jagath R. Junutula
ABSTRACT The antibody–drug conjugate (ADC) field has undergone a renaissance, with substantial recent developmental investment and subsequent drug approvals over the past 6 y. In November 2022, ElahereTM became the latest ADC to be approved by the US Food and Drug Administration (FDA). To date, over 260 ADCs have been tested in the clinic against various oncology indications. Here, we review the clinical
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Use of poxvirus display to select antibodies specific for complex membrane antigens mAbs (IF 5.3) Pub Date : 2023-08-27 Ernest S. Smith, Leslie A. Balch, Maria Scrivens, Shuying Shi, Wei Wang, Caroline D. Harvey, Angelica A. Cornelison, Malgorzata Gil-Moore, Renee A. Kirk, Loretta L. Mueller, Richard L. Hall, Alan P. Howell, Christine A. Reilly, Jessica M. Mayer, Francis G. Murante, Kari A Viggiani, Elaine M. Gersz, Holm Bussler, Madeleine R. Keefe, Elizabeth E. Evans, Mark J. Paris, Maurice Zauderer
ABSTRACT Antibody discovery against complex antigens is limited by the availability of a reproducible pure source of concentrated properly folded antigen. We have developed a technology to enable direct incorporation of membrane proteins such as GPCRs and into the membrane of poxvirus. The protein of interest is correctly folded and expressed in the cell-derived viral membrane and does not require
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Unique epitope–antibody interactions in the intrinsically disordered proteoglycan-like domain of human carbonic anhydrase IX defined by high-resolution NMR combined with yeast surface display mAbs (IF 5.3) Pub Date : 2023-08-25 Feng Ni, Cunle Wu, Ping Xu, Ping Wang, Yves Fortin, Melanie Arbour, Luke Masson, Denis L’Abbé, Andrea Acel, Mylene Gosselin, Anne E.G. Lenferink
ABSTRACT Carbonic anhydrase (CA)-IX is an extracellular enzyme that is essential in the adaptation of tumor cells to their increasingly more hypoxic and acidic microenvironment. Within the family of carbonic anhydrases, CA-IX is unique in that it is the only CA with an N-terminal intrinsically disordered region (IDR) containing a proteoglycan (PG)-like domain. This PG-like IDR has been described to
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A machine learning strategy for the identification of key in silico descriptors and prediction models for IgG monoclonal antibody developability properties mAbs (IF 5.3) Pub Date : 2023-08-23 Andrew B. Waight, David Prihoda, Rojan Shrestha, Kevin Metcalf, Marc Bailly, Marco Ancona, Talal Widatalla, Zachary Rollins, Alan C Cheng, Danny A. Bitton, Laurence Fayadat-Dilman
ABSTRACT Identification of favorable biophysical properties for protein therapeutics as part of developability assessment is a crucial part of the preclinical development process. Successful prediction of such properties and bioassay results from calculated in silico features has potential to reduce the time and cost of delivering clinical-grade material to patients, but nevertheless has remained an
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Targeted chain-exchange-mediated reconstitution of a split type-I cytokine for conditional immunotherapy mAbs (IF 5.3) Pub Date : 2023-08-22 Vedran Vasic, Can Buldun, Manfred Ritz, Steffen Dickopf, Guy J. Georges, Christian Spick, Alessa Peuker, Thomas Meier, Klaus Mayer, Ulrich Brinkmann
ABSTRACT Antibody-cytokine fusions targeted against tumor-associated antigens (TAAs) are promising cancer immunotherapy agents, with many such molecules currently undergoing clinical trials. However, due to the limited number of tumor-specific targets, on-target off-tumor effects can lead to systemic toxicity. Additionally, targeted cytokines can be scavenged by cytokine receptors on peripheral cells
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Monte Carlo Thompson sampling-guided design for antibody engineering mAbs (IF 5.3) Pub Date : 2023-08-21 Taro Kakuzaki, Hikaru Koga, Shuuki Takizawa, Shoichi Metsugi, Hirotake Shiraiwa, Zenjiro Sampei, Kenji Yoshida, Hiroyuki Tsunoda, Reiji Teramoto
ABSTRACT Antibodies are one of the predominant treatment modalities for various diseases. To improve the characteristics of a lead antibody, such as antigen-binding affinity and stability, we conducted comprehensive substitutions and exhaustively explored their sequence space. However, it is practically unfeasible to evaluate all possible combinations of mutations owing to combinatorial explosion when
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Selection of bispecific antibodies with optimal developability using FcRn‑Ph‑HPLC as an optimized FcRn affinity chromatography method mAbs (IF 5.3) Pub Date : 2023-08-20 Thomas Müller, Carolin Tasser, Michael Tesar, Ivica Fucek, Ute Schniegler-Mattox, Joachim Koch, Kristina Ellwanger
ABSTRACT A challenge when developing therapeutic antibodies is the identification of candidates with favorable pharmacokinetics (PK) early in development. A key determinant of immunoglobulin (IgG) serum half‑life in vivo is the efficiency of pH-dependent binding to the neonatal Fc receptor (FcRn). Numerous studies have proposed techniques to assess FcRn binding of IgG-based therapeutics in vitro, enabling
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Interplay of heavy chain introns influences efficient transcript splicing and affects product quality of recombinant biotherapeutic antibodies from CHO cells mAbs (IF 5.3) Pub Date : 2023-08-09 Emma Kelsall, Claire Harris, Titash Sen, Diane Hatton, Sarah Dunn, Suzanne Gibson
ABSTRACT Introns are included in genes encoding therapeutic proteins for their well-documented function of boosting expression. However, mis-splicing of introns in recombinant immunoglobulin (IgG) heavy chain (HC) transcripts can produce amino acid sequence product variants. These variants can affect product quality; therefore, purification process optimization may be needed to remove them, or if they