Article
Medicine, Research & Experimental
Maria U. Johansson, Christopher Weinert, Dietrich Alexander Reichardt, Dana Mahler, Dania Diem, Christian Hess, Diana Feusi, Simon Carnal, Julia Tietz, Noreen Giezendanner, Fabio Mario Spiga, David Urech, Stefan Warmuth
Summary: Upon reformatting antibody to single-chain variable fragment format, a previously hidden hydrophobic patch in the variable/constant domain interface becomes accessible for preexisting anti-drug antibody binding. To reduce the reactivity of preexisting antibodies and the exposed hydrophobic patch, mutations were introduced in this region. Through computational methods and experimental characterization, mutation of two threonine residues, Thr101 and Thr146, was found to be critical in eliminating preexisting antibody reactivity, which could have important implications in optimizing early drug development for antibody fragment-based therapeutics.
Review
Medicine, Research & Experimental
Yang Zhang
Summary: Antibody phage display technology is an important method for discovering monoclonal antibodies and has been widely used in the discovery of fully human antibodies. The technology has proven to be valuable with the approval of several top-selling antibody drugs.
Article
Medicine, Research & Experimental
Meiqi Yi, Jian Sun, Hanzi Sun, Yifei Wang, Shan Hou, Beibei Jiang, Yuanyuan Xie, Ruyue Ji, Liu Xue, Xiao Ding, Xiaomin Song, April Xu, Chichi Huang, Quan Quan, Jing Song
Summary: Aspartic acid (Asp) isomerization is a common post-translation modification observed in therapeutic antibodies, particularly in the Asp-Gly (DG), Asp-Ser (DS), and Asp-Thr (DT) motifs in structurally flexible regions. However, a study found unexpectedly high isomerization rate in the Asp-His (DHK) motif of monoclonal antibody mAb-a. The crystal structure analysis revealed the molecular mechanism behind this high isomerization rate, and it was found that the DHK motif should be removed in antibody therapeutics due to its impact on antibody activity and stability.
Article
Medicine, Research & Experimental
John P. P. Dowling, Pavel A. A. Nikitin, Fang Shen, Halley Shukla, James P. P. Finn, Nirja Patel, Cezary Swider, Jamie L. L. Bingaman-Steele, Chris Nicolescu, Eden L. Sikorski, Evan J. J. Greenawalt, Michael J. J. Morin, Matthew K. K. Robinson, Karen Lundgren, Benjamin C. C. Harman
Summary: Immune checkpoint inhibitors have revolutionized cancer treatment, but they only work for a small subset of patients. Targeting suppressive mechanisms acting on innate immune cells can improve clinical response by activating adaptive and innate immune systems. The study shows that IL-38 is expressed in a high percentage of cancer patients and allows tumor cells to suppress anti-tumor immunity. Blocking IL-38 with IMM20324 can re-activate immunostimulatory mechanisms, induce immune memory, and inhibit tumor growth.
Article
Medicine, Research & Experimental
Monica L. Fernandez-Quintero, Janik Kokot, Franz Waibl, Anna-Lena M. Fischer, Patrick K. Quoika, Charlotte M. Deane, Klaus R. Liedl
Summary: The increased availability of high-quality experimental structural data and advances in structural biology have driven research on predicting protein structures. In 2020, AlphaFold2 revolutionized the field by combining artificial intelligence with evolutionary information from multiple sequence alignments. Accurate protein structure models are crucial for biophysical property predictions and antibody design. However, it is important to be aware of potential inaccuracies in protein structure models, particularly in antibody models, such as incorrect bonds and stereochemistry. We emphasize the need to carefully review these models before further computational analysis and experimental studies. To aid in assessing model quality, we provide a tool called TopModel for validating structure models.
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.
Review
Medicine, Research & Experimental
Indrajit Ghosh, Hiten Gutka, Mary E. Krause, Ryan Clemens, Ramesh S. Kashi
Summary: Three critical aspects that define high concentration antibody products (HCAPs) are formulation composition, dosage form, and primary packaging configuration. Technical challenges, such as physical and chemical instability, viscosity, delivery volume limitations, and product immunogenicity, can hinder successful development and commercialization of HCAPs. Robust formulation and process development strategies, as well as rational selection of excipients and packaging components, can overcome these challenges and enable the development of improved HCAPs.
Article
Medicine, Research & Experimental
Xiaoding Tan, Peng Fang, Kaiying Li, Meng You, Yuxia Cao, Hui Xu, Xiaohong Zhu, Lu Wang, Xin Wei, Haiying Wen, Wendi Li, Lei Shi, Xiaowei Sun, Dongan Yu, Huikai Zhu, Zhenzhen Wang, Datao Liu, Hui Shen, Wei Zhou, Maomao An
Summary: We designed and developed a novel DNA topoisomerase I inhibitor MF-6, which demonstrated stronger cytotoxicity and inducible immunogenic cell death compared to DXd. To harness MF-6's ability to induce antitumor immunity, we developed a HER2-targeted antibody-drug conjugate (ADC) called trastuzumab-L6, which included a cleavable linker and MF-6. Trastuzumab-L6 exhibited enhanced antitumor efficacy by inducing immune response, activating dendritic cells and cytotoxic CD8+ T cells to acquire adaptive immune memory.
Article
Medicine, Research & Experimental
Ameya Harmalkar, Roshan Rao, Yuxuan Richard Xie, Jonas Honer, Wibke Deisting, Jonas Anlahr, Anja Hoenig, Julia Czwikla, Eva Sienz-Widmann, Doris Rau, Austin J. Rice, Timothy P. Riley, Danqing Li, Hannah B. Catterall, Christine E. Tinberg, Jeffrey J. Gray, Kathy Y. Wei
Summary: Over the past three decades, there has been a growing interest in monoclonal antibodies (mAbs) as therapeutics, especially multispecific biologics (msAbs) that engage distinct targets. However, the poor thermostability of single-chain variable fragments (scFv) has hindered their development. To address this, machine learning approaches using pre-trained language models and convolutional neural networks were utilized to classify thermostable scFv variants from sequence, showing promising results in predicting stability.
Article
Medicine, Research & Experimental
Tsega L. Solomon, Frank Delaglio, John P. Giddens, John P. Marino, Yihua Bruce Yu, Marc B. Taraban, Robert G. Brinson
Summary: The clinical efficacy and safety of protein-based drugs rely on the integrity of the protein higher order structure (HOS). Establishing metrics for quality attributes of mAb therapeutics through high-resolution techniques is necessary. In this study, a forced degradation method was used to evaluate the effects on HOS using the model biotherapeutic NISTmAb. The combination of NMR with other analytical tools allows for the monitoring of oxidation kinetics and extraction of resulting structural changes in functionally relevant mAbs.
Article
Medicine, Research & Experimental
Baoshan Zhang, Jason Gorman, Young D. Kwon, Amarendra Pegu, Cara W. Chao, Tracy Liu, Mangaiarkarasi Asokan, Michael F. Bender, Tatsiana Bylund, Leland Damron, Deepika Gollapudi, Paula Lei, Yile Li, Cuiping Liu, Mark K. Louder, Krisha McKee, Adam S. Olia, Reda Rawi, Arne Schon, Shuishu Wang, Eun Sung Yang, Yongping Yang, Kevin Carlton, Nicole A. Doria-Rose, Lawrence Shapiro, Michael S. Seaman, John R. Mascola, Peter D. Kwong
Summary: Antibody CAP256-VRC26.25 targets the second hypervariable region (V2) with extraordinary neutralization potency, but limited breadth. By linking CAP256V2LS to the llama nanobody J3, the bispecific antibody exhibited improved breadth and potency through synergistic neutralization.
Review
Medicine, Research & Experimental
Gaoming Liu, Jun Wei, Wenfeng Xiao, Wenqing Xie, Qin Ru, Lin Chen, Yuxiang Wu, Ali Mobasheri, Yusheng Li
Summary: Degenerative musculoskeletal disorders are age-related diseases that severely affect patients' ability to work and can have serious consequences. Notch signaling pathway plays a crucial role in these disorders, retarding the progress of degeneration and having important functions in stem/progenitor cells.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Medicine, Research & Experimental
Jingrong Liu, Hongjie Fan, Xinmiao Liang, Yang Chen
Summary: The Polycomb Repressor Complex (PRC) plays a crucial role in gene regulation and its interaction with cellular signaling pathways sheds light on the complexity of cancer. Dysregulation of the PRC complex is significant in various tumors and understanding the underlying mechanisms driving cancer progression is important. The development of therapeutic strategies targeting PRC complexes, particularly EZH2 inhibitors, has made significant advancements and combination therapies may enhance targeted treatments efficacy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Misun Kim, Heung Joo Yuk, Yueun Min, Dong-Seon Kim, Yoon-Young Sung
Summary: Securinega suffruticosa extract attenuates atopic dermatitis and has potential as a therapeutic natural product candidate for AD.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Wei -shun Tian, Jing Zhao, Myung-Kon Kim, Hyun-Jin Tae, In-Shik Kim, Dongchoon Ahn, Hong Pil Hwang, Ming-xian Mao, Byung-Yong Park
Summary: This study demonstrated that Veronica persica has hepatoprotective abilities on acetaminophen-induced acute liver injury (ALI), primarily by alleviating oxidative stress and inflammation through suppressing the phosphorylation of NF-kappa B/STAT3 cascade and ERK-JNK and inducing AMPK activation.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Jianzheng He, Shuzhen Han, Yixuan Wang, Qian Kang, Xiaoqian Wang, Yun Su, Yaling Li, Yongqi Liu, Hui Cai, Minghui Xiu
Summary: Chemotherapy drug CPT-11 leads to various side effects in patients, including delayed development, imbalance in offspring gender ratio, shortened lifespan, impaired locomotor ability, changed metabolic capacity, ovarian atrophy, and increased excretion. It also causes intestinal damages, such as decreased intestinal length, disrupted gastrointestinal acid-based homeostasis, epithelial cell death, and damaged ultrastructure and mitochondria of epithelial cells. CPT-11 induces intestinal damage mainly through regulating several signaling pathways and increasing ROS accumulation.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Celine Konecki, Jed Hadjoudj, Federica Tralongo, Cyril Haudecoeur, Claire Gozalo, Aurelie Fouley, Helene Marty, Catherine Feliu, Zoubir Djerada
Summary: The study developed and validated a fast, simple, and sensitive method for the simultaneous quantification of multiple psychotropic drugs. This method has been successfully used for therapeutic drug monitoring in psychiatric patients, particularly those taking multiple medications.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Jinfeng Sun, Liwei Li, Li Xiong, Fan Chen, Lingyu She, Hao Tang, Yuqing Zeng, Ying Duan, Luyao Li, Wei Wang, Gao Li, Xia Zhao, Guang Liang
Summary: Alzheimer's disease (AD) is a common age-related neurodegenerative disorder, and natural compounds from traditional medicine and plant origins may provide new approaches for its treatment. This study found that Parthenolide (PTN) has the potential to treat AD. In vitro results showed that PTN reduced apoptosis, decreased reactive oxygen species (ROS) production, and restored mitochondrial membrane potential in PC12 cells. Furthermore, PTN treatment improved spatial learning and memory deficits in a murine model of AD. Mechanistically, PTN's neuroprotective effects are attributed to its regulation of the AMPK/GSK3 beta (ser9)/Nrf2 signaling pathway and protection against ROS-related apoptosis in neuronal cells.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Luting Yu, Yihan Zhou, Shaozheng Sun, Runlin Wang, Weihong Yu, Hanyu Xiao, Zhuxi Yu, Chen Luo
Summary: This study investigates the relationship between Reg3A expression, colorectal cancer (CRC) development, and immune cell alteration in patients. The results show that high expression of Reg3A is associated with CRC and increased immune cell infiltration. Reg3A overexpression inhibits cell proliferation and promotes apoptosis, leading to a tumor-suppressive effect. Additionally, Reg3A activates and recruits T cells, resulting in cytotoxic tumor suppression.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Zihui Zheng, Zhaoshun Qiu, Xiyu Xiong, Aobo Nie, Wenzhao Zhou, Huimin Qiu, Huanhuan Zhao, Huiwen Wu, Jun Guo
Summary: This study reveals the important role of protein nanoparticles in ischemia-induced cerebral edema, which causes cell swelling by regulating sodium/chloride ion channels and increased osmotic pressure through electrochemical-tension signal transduction. The study also found that enhanced sensitivity in sodium and chloride ion channels plays a crucial role in cerebral edema.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
