Article
Chemistry, Analytical
Bastiaan L. Duivelshof, Alain Beck, Davy Guillarme, Valentina D'Atri
Summary: Bispecific antibodies are an important class of biopharmaceutical drugs, with chain-association being a critical challenge in their development and production. This study developed an analytical workflow using various chromatographic modes combined with high resolution mass spectrometry, and successfully applied it to Hemlibra (emicizumab).
Review
Environmental Sciences
Aikaterini A. Zompra, Styliani A. Chasapi, Matthew S. Twigg, Karina Salek, Ioannis Anestopoulos, Alex Galanis, Aglaia Pappa, Tony Gutierrez, Ibrahim M. Banat, Roger Marchant, Stephen R. Euston, Mihalis I. Panayiotidis, Georgios A. Spyroulias
Summary: Synthetic surfactants, commonly used in various industries, have a negative impact on the environment due to their synthetic preparation. As a result, there is a growing interest in exploring natural sources of surfactants, which can be produced through environmentally friendly processes. Microbial production of such chemicals, however, often results in crude materials composed of multiple complex bioproducts. Therefore, advanced analytical methods are required for the extraction, identification, and characterization of biosurfactants.
FRONTIERS IN MARINE SCIENCE
(2022)
Article
Medicine, Research & Experimental
Florian Heinkel, Meghan M. Verstraete, Siran Cao, Janessa Li, Patrick Farber, Elizabeth Stangle, Begonia Silva-Moreno, Fangni Peng, Surjit Dixit, Martin J. Boulanger, Thomas Spreter Von Kreudenstein, Eric Escobar-Cabrera
Summary: The newly developed heterodimeric IgA Fc platform allows for the development of novel, multifunctional, and multimeric molecules that have the potential to transform the next generation of antibody therapeutics.
Article
Multidisciplinary Sciences
Katherine E. Harris, Kyle J. Lorentsen, Harbani K. Malik-Chaudhry, Kaitlyn Loughlin, Harish Medlari Basappa, Sharon Hartstein, Ghenima Ahmil, Nicole S. Allen, Brian C. Avanzino, Aarti Balasubramani, Andrew A. Boudreau, Karen Chang, Maria-Cristina Cuturi, Laura M. Davison, Dennis M. Ho, Suhasini Iyer, Udaya S. Rangaswamy, Preethi Sankaran, Ute Schellenberger, Roland Buelow, Nathan D. Trinklein
Summary: The study introduces a novel bispecific heavy-chain only antibody that binds to and activates signaling through the heterodimeric IL-2R beta gamma receptor complex on resting T-cells and NK cells, offering a safe and effective alternative to traditional IL-2 therapy with enhanced therapeutic potential for cancer treatment.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Jun Lin, Mengyu Xie, Dan Liu, Zhen Gao, Xiaoyan Zhao, Hongxia Ma, Sheng Ding, Shu mei Li, Song Li, Yanling Liu, Fang Zhou, Hao Hu, Tao Chen, He Chen, Min Xie, Bo Yang, Jun Cheng, Mingjun Ma, Yanyang Nan, Dianwen Ju
Summary: An aberrant peak near the light chain (LC) was observed during the development of a bispecific antibody (BsAb) product, and further analysis revealed that it was caused by a sequence variant resulting from aberrant splicing at the transcription level.
FRONTIERS IN CHEMISTRY
(2022)
Article
Biology
Satish Rojekar, Anusha R. Pallapati, Judit Gimenez-Roig, Funda Korkmaz, Farhath Sultana, Damini Sant, Clement M. Haeck, Anne Macdonald, Se-Min Kim, Clifford J. Rosen, Orly Barak, Marcia Meseck, John Caminis, Daria Lizneva, Tony Yuen, Mone Zaidi
Summary: In this article, researchers report the development of a unique formulation for the FSH-blocking humanized antibody MS-Hu6, which shows potential for treating osteoporosis, obesity, and Alzheimer's disease. Through a series of experiments, they demonstrate that the formulation maintains thermal stability, monomeric stability, and colloidal stability at high concentrations, and is manufacturable and transportable. This study provides important insights for developing biologic formulations in academic medical centers.
Article
Immunology
Sebastian Lutz, Katja Klausz, Anca-Maria Albici, Lea Ebinger, Lea Sellmer, Hannah Teipel, Andre Frenzel, Anna Langner, Dorothee Winterberg, Steffen Krohn, Michael Hust, Thomas Schirrmann, Stefan Duebel, Regina Scherliess, Andreas Humpe, Martin Gramatzki, Christian Kellner, Matthias Peipp
Summary: This study successfully activated natural killer cells and induced lysis of lymphoma cells by preparing novel bispecific antibodies. The study also found that co-administration with specific monoclonal antibodies or bispecific T cell engagers enhanced antibody-dependent cell-mediated cytotoxicity and T cell activation. Furthermore, the study proposed a combinatorial approach targeting multiple tumor antigens, which has the potential to optimize antibody cancer therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Applied
Xiaoqing Ma, Yangying Sun, Daodong Pan, Jinxuan Cao, Yali Dang
Summary: Phosphorylation modification by STP can enhance the stability of hemoglobin through structural changes, making phosphorylated NO-Hb more stable than NO-Hb in various conditions. Absorbance of P-NO-Hb is higher and decreases more slowly over time compared to Hb and NO-Hb.
Article
Biochemistry & Molecular Biology
Johanna Voigt, Christoph Meyer, Frank Bordusa
Summary: Bispecific antibodies (bsAbs) are emerging as a leading class of immunotherapies for cancer treatment. This study presents novel chemo-enzymatic and purely enzymatic strategies for generating bispecific antibody fragments, which show promising results in breast cancer cell lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Da Chen, Yingjie Zhao, Mingyu Li, Hang Shang, Na Li, Fan Li, Wei Wang, Yuan Wang, Ruina Jin, Shiyu Liu, Xun Li, Shan Gao, Yujie Tian, Ruonan Li, Huanhuan Li, Yongyan Zhang, Mingjuan Du, Youjia Cao, Yan Zhang, Xin Li, Yi Huang, Liaoyuan A. Hu, Fubin Li, Hongkai Zhang
Summary: Fc engineering has become a focus in antibody drug development. A mammalian cell display-based platform was developed to screen millions of Fc variants for optimized binding to Fc gamma RIIIa or Fc gamma RIIb. Novel Fc variants with enhanced binding and improved effector function were successfully identified.
Article
Immunology
Carina Lynn Gehlert, Pegah Rahmati, Ammelie Svea Boje, Dorothee Winterberg, Steffen Krohn, Thomas Theocharis, Elisa Cappuzzello, Anja Lux, Falk Nimmerjahn, Ralf J. Ludwig, Marta Lustig, Thies Roesner, Thomas Valerius, Denis Martin Schewe, Christian Kellner, Katja Klausz, Matthias Peipp
Summary: This study engineered a CD19 antibody to enhance effector cell-mediated killing and CDC activity. The dual optimized CD19 antibody showed improved ADCC, ADCP, and CDC compared to the non-engineered antibody. This finding is crucial for improving CD19-directed cancer immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Cindy Rodriguez, Samantha Delaney, Samantha M. Sarrett, Outi M. Keinanen, Brian M. Zeglis
Summary: This article introduces the application of antibody engineering in nuclear medicine and explores how it can be used to improve the performance of radioimmunoconjugates.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Medicine, Research & Experimental
Bo Zhao, Yunlong Zhao, Stephanie Adaniya, Yue Fu, Youmi Moon, Justin Heftel, Shuzhen Chen, Hui Xiao, Ning Li
Summary: The development of novel bispecific antibody (bsAb) platforms provides unprecedented opportunities for therapeutic applications, but the expression and manufacturing of desired bsAbs can be challenging. Therefore, more comprehensive and customized structural characterization is important to understand the reactivity of bsAbs and guide process development and manufacturing. In this study, the Regeneron bsAb platform was characterized using hydrogen deuterium exchange mass spectrometry (HDX-MS), revealing structural deprotection and decreased conformational stability in the Fc domain due to site-specific substitutions. Additionally, the introduction of substitutions resulted in a slight reduction in binding affinity to FcRn. The detailed structural elucidation by HDX-MS improves understanding of the structure-property relationship of the Regeneron bsAb format, aiding in process development, risk assessment, and manufacturing.
Article
Oncology
Justin T. Huckaby, Elisa Landoni, Timothy M. Jacobs, Barbara Savoldo, Gianpietro Dotti, Samuel K. Lai
Summary: The study demonstrates the in vivo engineering of CAR-T cells using a redirected lentiviral system that offers exceptional specificity and efficiency in controlling the growth of aggressive B cell tumors, highlighting the promising approach for personalized cancer immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Chemistry, Analytical
Armaghan Shafaei, Joanna Rees, Claus T. Christophersen, Amanda Devine, David Broadhurst, Mary C. Boyce
Summary: This study presents a simple extraction method for the analysis of bile acids in feces, followed by quantification using liquid chromatography and tandem mass spectrometry. The method shows good precision and accuracy, making it suitable for large-scale analysis of fecal samples.
ANALYTICA CHIMICA ACTA
(2021)
Article
Substance Abuse
David Eddie, Brandon G. Bergman, Lauren A. Hoffman, John F. Kelly
Summary: This study examines the relationship between continued substance use after resolving an alcohol or other drug problem and abstinence, and finds that lower-risk substance use is associated with better functioning and greater well-being.
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Roxana Roshankhah, Guoqiang Chen, Yating Xu, Nikhila Butani, Yves Durocher, Robert Pelton, Raja Ghosh
Summary: This study examines the purification of Trastuzumab using cation-exchange z(2) laterally-fed membrane chromatography (z(2)LFMC). The results show that the z(2)LFMC process is comparable to protein A affinity chromatography in terms of purity and recovery, but it is faster and does not require acidic conditions. The productivity of Trastuzumab with the z(2)LFMC process is more than 3 times higher than with column-based purification. Therefore, z(2)LFMC could be a cheaper and more efficient alternative to protein A affinity chromatography.
BIOCHEMICAL ENGINEERING JOURNAL
(2022)
Article
Engineering, Chemical
Sebastian Juan Reyes, Yves Durocher, Phuong Lan Pham, Olivier Henry
Summary: The growing biopharmaceutical industry has enabled the monitoring of key variables for process characterization and outcome predictions. Technological innovation in sensing technologies allows for continuous online monitoring of quality attributes, leading to improved process control and outcome prediction. This paper reviews state-of-the-art sensing technologies and their applications in cell culture monitoring, emphasizing the push towards industry 4.0 and smart manufacturing in the biopharmaceutical sector.
Article
Biotechnology & Applied Microbiology
Simon Joubert, Julie Guimond, Sylvie Perret, Felix Malenfant, S. Mehdy Elahi, Anne Marcil, Marie Parat, Michel Gilbert, Anne E. G. Lenferink, Jason Baardsnes, Yves Durocher
Summary: A method to enhance the effector function of antibodies and increase their antitumor activity by inhibiting core fucosylation is discussed. The expression of a membrane-associated anti-FUT8 intrabody in the endoplasmic reticulum and Golgi apparatus reduces FUT8 enzyme activity and core fucosylation of antibody N-glycans, resulting in antibodies with enhanced ADCC effector function.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Biotechnology & Applied Microbiology
Izel Koyuturk, Surbhi Kedia, Anna Robotham, Alexandra Star, Denis Brochu, Janelle Sauvageau, John Kelly, Michel Gilbert, Yves Durocher
Summary: Alpha-1-antitrypsin (A1AT) is a protease inhibitor that protects the lungs from damage. A1AT deficiency increases the risk of lung diseases. Currently, the only treatment is weekly injection of plasma-purified A1AT. This study aimed to produce recombinant A1AT with N-glycans similar to plasma-derived A1AT. By disrupting glycosyltransferase genes and overexpressing sialyltransferase, high levels of recombinant A1AT with desired glycosylation were obtained.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Biochemical Research Methods
Raja Ghosh, Geoff Hale, Yves Durocher, Paul Gatt
Summary: This study describes a simple dry-compression technique for preparing a flat cuboid chromatography device and discusses its application in fast protein separation. The device allows the separation of binary protein mixtures in a short amount of time, while simultaneously increasing productivity and purity. The suitability of the device for preparative protein separations is demonstrated through the purification of a monoclonal antibody from cell culture supernatant.
JOURNAL OF CHROMATOGRAPHY A
(2022)
Article
Substance Abuse
Audrey Hang Hai, Sehun Oh, Catalina Lopez-Quintero, Christina S. Lee, John F. Kelly, Michael G. Vaughn, Christopher P. Salas-Wright
Summary: This report aims to identify the psycho-socio-behavioral profiles of US mutual help group (MHG) participants. The study used data from the National Survey on Drug Use and Health to identify three latent classes: low-risk group, psychological distress group, and criminal justice system involvement group. The results showed differences in sociodemographic characteristics and behavioral risks among the three classes. The study suggests tailoring MHG referrals based on the specific profiles of participants to enhance effectiveness.
SUBSTANCE USE & MISUSE
(2022)
Article
Biochemical Research Methods
Nikhila Butani, Yating Xu, Si Pan, Yves Durocher, Raja Ghosh
Summary: Recombinant SARS-CoV-2 trimeric spike protein, a potential COVID-19 vaccine candidate, is challenging to manufacture on a large scale due to its size. A membrane chromatography-based purification method is proposed in this paper, which provides a fast and scalable approach for manufacturing the spike protein.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Article
Medicine, Research & Experimental
Maria L. Jaramillo, Traian Sulea, Yves Durocher, Mauro Acchione, Melissa J. Schur, Anna Robotham, John F. Kelly, Marie-France Goneau, Alma Robert, Yuneivy Cepero-Donates, Michel Gilbert
Summary: Effective processes for synthesizing antibody-drug conjugates (ADCs) require site-specific incorporation of the payload, optimal drug/antibody ratio, and a homogeneous product. Conventional ADCs often face issues like interference with epitope binding and product heterogeneity. This study presents a more controlled process where the drug is specifically conjugated to Fab N-linked glycans, resulting in ADCs with desired drug/antibody ratio and efficient targeting.
Article
Medicine, General & Internal
John F. Kelly, Samuel A. Levy, Bettina B. Hoeppner
Summary: Alcohol use disorder (AUD) is a widespread psychiatric illness with significant health and economic burden. In addition to professional treatments, mutual-help organizations like Alcoholics Anonymous (AA) and Self-Management and Recovery Training (SMART Recovery) play important roles. This study aims to explore the patterns and benefits of SMART Recovery and investigate its moderators and mechanisms in conferring recovery benefits.
Article
Immunology
Mariam Maltseva, Yannick Galipeau, Tyler M. Renner, Lise Deschatelets, Yves Durocher, Bassel Akache, Marc-Andre Langlois
Summary: Continuous viral evolution of SARS-CoV-2 has led to variants capable of immune evasion, vaccine breakthrough infections, and increased transmissibility. Intranasal administration of adjuvanted protein subunit vaccines can induce robust immune responses in mice, producing antibodies against the virus.
Article
Medicine, Research & Experimental
Seyed Farzad Baniahmad, Romane Oliverio, Ines Obregon-Gomez, Alma Robert, Anne E. G. Lenferink, Elena Pazos, Nick Virgilio, Xavier Banquy, Gregory De Crescenzo, Yves Durocher
Summary: Long-term delivery is a successful strategy to reduce adverse effects of mAb-based treatments. Macroporous hydrogels and affinity-based strategies are effective in sustained and localized delivery of mAbs. The Ecoil and Kcoil peptides have high-affinity binding and can be used for controlled release of Ecoil-tagged trastuzumab from macroporous hydrogels.
Article
Substance Abuse
Samuel N. Meisel, Emily A. Hennessy, Jordan Jurinsky, John F. Kelly
Summary: Social recovery capital is the combination of social resources that can be used to initiate and sustain addiction recovery through social support. Understanding the role and measurement of social recovery capital is important for enhancing recovery outcomes, but more research is needed to fully utilize this concept.
ADDICTION RESEARCH & THEORY
(2023)
Article
Substance Abuse
John F. Kelly, Samuel Levy, Maya Matlack, Bettina B. Hoeppner
Summary: This study found that SMART Recovery attracts individuals with greater psychosocial stability and economic advantage, as well as less severe histories of alcohol-related impairment and legal involvement. These findings suggest that the SMART organization may provide an additional recovery option that caters to the characteristics and needs of this population.
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2023)
Article
Immunology
Karen Colwill, Yannick Galipeau, Matthew Stuible, Christian Gervais, Corey Arnold, Bhavisha Rathod, Kento T. Abe, Jenny H. Wang, Adrian Pasculescu, Mariam Maltseva, Lynda Rocheleau, Martin Pelchat, Mahya Fazel-Zarandi, Mariam Iskilova, Miriam Barrios-Rodiles, Linda Bennett, Kevin Yau, Francois Cholette, Christine Mesa, Angel X. Li, Aimee Paterson, Michelle A. Hladunewich, Pamela J. Goodwin, Jeffrey L. Wrana, Steven J. Drews, Samira Mubareka, Allison J. McGeer, John Kim, Marc-Andre Langlois, Anne-Claude Gingras, Yves Durocher
Summary: This study describes a scalable solution to detect and quantify SARS-CoV-2 antibodies, discriminate between natural infection and vaccination-induced responses, and assess the inhibitory effect of antibodies on ACE2-spike interaction. They developed methods and reagents for antibody detection using ELISA and snELISA, enabling large-scale analysis. In addition, they provided detailed protocols for the experiments.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2022)