Article
Medicine, Research & Experimental
Roope A. Kallionpaa, Sirkku Peltonen, Kim My Le, Eija Martikkala, Mira Jaaskelainen, Elnaz Fazeli, Pilvi Riihila, Pekka Haapaniemi, Anne Rokka, Marko Salmi, Ilmo Leivo, Juha Peltonen
Summary: This study investigated the immune microenvironment of cutaneous neurofibromas (cNFs) in patients with neurofibromatosis 1 (NF1). The results showed that cNFs have substantial populations of T cells and macrophages, which may be tumor-specific. T cell populations in cNFs were found to be different from those in the skin, and cNFs exhibited lower expression of proteins related to T cell-mediated immunity compared to the skin.
LABORATORY INVESTIGATION
(2024)
Article
Medicine, Research & Experimental
Connor Celum, Bethany Jablonski Horton, Mark Conaway
Summary: This paper proposes a phase-I clinical trial design that uses ordinal toxicity to locate group-specific doses. The proposed method avoids dose-reversals and is compared with two other methods through simulations.
CONTEMPORARY CLINICAL TRIALS
(2024)
Review
Biochemistry & Molecular Biology
Nikoleta Bizymi, Andreas M. Matthaiou, Irene Mavroudi, Aristea Batsali, Helen A. Papadaki
Summary: Myeloid-derived suppressor cells (MDSCs) are innate immune cells that have immunomodulatory properties. They interact extensively with other innate or adaptive immune cells and can either enhance or attenuate immune responses depending on the triggering conditions. However, their positive role in host defense mechanisms is rarely discussed in the literature.
Review
Nanoscience & Nanotechnology
Marco Felipe Salas-Orozco, Ana Cecilia Lorenzo-Leal, Idania de Alba Montero, Nuria Patino Marin, Miguel Angel Casillas Santana, Horacio Bach
Summary: The emergence of antibiotic-resistant bacteria in severe infections is a growing concern, particularly in hospital environments. Metal-based nanomaterials have shown potential as an alternative to combat these bacteria, but there is a risk of bacterial resistance and environmental accumulation.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2024)
Article
Medicine, Research & Experimental
Tanya Knutzen, Eileen Bulger, Matt Iles-Shih, Alexandra Hernandez, Allison Engstrom, Lauren Whiteside, Navneet Birk, Khadija Abu, Jake Shoyer, Cristina Conde, Paige Ryan, Jin Wang, Joan Russo, Patrick Heagerty, Larry Palinkas, Douglas Zatzick
Summary: This study aims to investigate how trauma centers in the US can effectively conduct mental health screening, intervention, and referral services to help injured patients recover. The study will randomly assign patients to different intervention groups and compare the impact of different interventions on PTSD symptoms and emergency department/inpatient utilization.
CONTEMPORARY CLINICAL TRIALS
(2024)
Article
Biochemistry & Molecular Biology
Binbin Chang, Zhang Wang, Hui Cheng, Tingyuan Xu, Jieyu Chen, Wan Wu, Yizhi Li, Yong Zhang
Summary: Acacetin can attenuate sepsis-induced ALI by inhibiting the inflammatory response and promoting macrophage polarization. This study is of great significance for the development of new treatments for sepsis-induced ALI.
Article
Medicine, Research & Experimental
John D. Bagert, Vaheh Oganesyan, Chi- 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
Summary: Bispecific antibodies are increasingly used in therapeutic development due to their expanded capabilities. This study presents enhancements to the DuetMab platform, which improves the production of correctly assembled bispecific antibodies. The introduction of electrostatic steering mutations at the C(H)1-C-L interface with lambda light chains improves chain pairing and production, enabling reliable production of bispecific antibodies with diverse Fv sequences.
Review
Medicine, Research & Experimental
Heather Maecker, Vidya Jonnalagadda, Sunil Bhakta, Vasu Jammalamadaka, Jagath R. Junutula
Summary: The ADC field has experienced a renaissance with recent investment and regulatory approvals. A total of 260 ADCs have been tested in clinical trials for cancer treatment. This review focuses on FDA-approved ADCs (11), ADCs in clinical trials but not yet approved (164), and discontinued candidates (92). Analysis based on tumor antigen targeting, linker, payload choices, and clinical stage achieved is provided, with discussion on biologic engineering modifications that can improve therapeutic index and increase regulatory approvals.
Review
Medicine, Research & Experimental
Mengzhen Jiang, Man Liu, Guodi Liu, Jiawen Ma, Lixin Zhang, Shenlin Wang
Summary: Antibody-based immune checkpoint blockade (ICB) is an effective clinical application for cancers. It can reverse the phenotype of depleted activated T cells and recover their anti-tumoral activities. High-resolution structures of the therapeutic monoclonal antibodies with PD-1 or PD-L1 have revealed the key inter-molecular interactions and provided valuable insights into the fundamental mechanisms by which these antibodies inhibit PD-L1-PD-1 binding.
Article
Medicine, Research & Experimental
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
Summary: Identification of favorable biophysical properties for protein therapeutics is crucial for preclinical development. Predicting these properties and bioassay results from computational features has potential to reduce time and cost, but remains a challenge. This study demonstrates an automated machine learning workflow using physiochemical features to generate predictive models for key developability endpoints. The discovered features validate previous literature and suggest directions for further research and model improvement.
Article
Medicine, Research & Experimental
Hans Peter Grimm, Vanessa Schumacher, Martin Schaefer, Sabine Imhof-Jung, Per-Ola Freskgard, Kevin Brady, Carsten Hofmann, Petra Rueger, Tilman Schlothauer, Ulrich Goepfert, Maximilian Hartl, Sylvia Rottach, Adrian Zwick, Shanon Seger, Rachel Neff, Jens Niewoehner, Niels Janssen
Summary: This study investigates a fusion protein composed of gantenerumab and a brainshuttle module for the treatment of Alzheimer's disease. The protein showed good tolerance and increased distribution in the brain, with 4-18 times higher exposure compared to gantenerumab. The study also predicts dosing regimens for effective amyloid reduction based on brain exposure modeling.
Article
Medicine, Research & Experimental
Britta Lipinski, Laura Unmuth, Paul Arras, Stefan Becker, Christina Bauer, Lars Toleikis, Simon Krah, Achim Doerner, Desislava Yanakieva, Ammelie Svea Boje, Katja Klausz, Matthias Peipp, Vanessa Siegmund, Andreas Evers, Harald Kolmar, Lukas Pekar, Stefan Zielonka
Summary: In this study, bispecific antibody derivatives mimicking the function of IL-18 were generated using single domain antibodies targeting IL-18 Ra and IL-18 R ss. By engineering the structure, IL-18 mimetics with significantly augmented functionalities, triggering proinflammatory cytokine release more potently than IL-18, were generated. This strategy enables the generation of IL-18 mimetics with tailor-made cytokine functionalities.
Article
Medicine, Research & Experimental
Xinghua Pang, Zhaoliang Huang, Tingting Zhong, Peng Zhang, Zhongmin Maxwell Wang, Michelle Xia, Baiyong Li
Summary: Clinical studies have confirmed that the combination therapy of antibodies targeting CTLA-4 and PD-1 significantly enhances clinical benefit compared to the use of PD-1 antibody alone. However, limited application of this combination is due to toxicities. Cadonilimab, a tetravalent bispecific antibody, demonstrates similar biological activity as the combination therapy and exhibits higher binding avidity in high-density PD-1 and CTLA-4 environments. Its Fc-null design reduces toxic side effects. These features make cadonilimab a potential candidate for improving both safety and anti-tumor efficacy.
Article
Medicine, Research & Experimental
Andreas V. Madsen, Peter Kristensen, Alexander K. Buell, Steffen Goletz
Summary: This study demonstrates a simple and efficient method to generate high-quality bsAbs with both binding functionalities intact by fusing sdAbs onto IgG scaffolds through flexible linkers. By systematically comparing sdAb fusion strategies, the results show that fusion of sdAbs to the heavy chain promotes good expression, stability, and efficient binding to both antigens. The study also provides a toolbox of complementary methods for in-depth analysis of key features, such as dual antigen binding and stability, to ensure high bsAb quality.
Article
Medicine, Research & Experimental
Hikaru Koga, Takashi Yamano, Juan Betancur, Satoko Nagatomo, Yousuke Ikeda, Kazuki Yamaguchi, Yoshiaki Nabuchi, Kazuki Sato, Yuri Teranishi-Ikawa, Motohiko Sato, Hiroyuki Hirayama, Akira Hayasaka, Takuya Torizawa, Kenta Haraya, Zenjiro Sampei, Hirotake Shiraiwa, Takehisa Kitazawa, Tomoyuki Igawa, Taichi Kuramochi
Summary: Efficient production of bispecific antibodies (BsAbs) is crucial, and we developed the FAST-Ig technology to achieve high efficiency and correct pairing of heavy chains (HCs) and light chains (LCs) by introducing charged amino-acid substitutions at the HC/LC interface.
Review
Medicine, Research & Experimental
Tushar Jain, Todd Boland, Maximiliano Vasquez
Summary: With the increasing importance of antibodies as therapeutic agents, it is crucial to identify developability risks early in the development process. Various high-throughput in vitro assays and in silico approaches have been proposed to mitigate these risks. This review analyzes published experimental assessments and computational metrics for clinical antibodies and finds that in vitro measurements of polyspecificity and hydrophobicity are more predictive of clinical progression than in silico counterparts. It also highlights the challenges of model generalization and the reproducibility of computed metrics.
Article
Medicine, Research & Experimental
Susanne Klint, Joachim Feldwisch, Lindvi Gudmundsdotter, Karin Dillner Bergstedt, Elin Gunneriusson, Ingmarie Hoiden Guthenberg, Anders Wennborg, Andrew C. C. Nyborg, Amol P. P. Kamboj, Paul M. M. Peloso, David Bejker, Fredrik Y. Y. Frejd
Summary: In this study, a novel small biological molecule, izokibep, was developed using Affibody technology to inhibit IL-17A signaling. Preclinical studies showed that izokibep selectively inhibits human IL-17A with superior potency and efficacy compared to anti-IL-17A mAbs. Phase 1 clinical trials demonstrated the safety and efficacy of izokibep in treating psoriasis.
Article
Medicine, Research & Experimental
Paul Cain, Lihua Huang, Yu Tang, Victor Anguiano, Yiqing Feng
Summary: IgG-based monoclonal antibody therapeutics have dominated the biotherapeutics field for decades. However, there is a lack of systematic evaluation of different IgG subclasses on manufacturability and long-term stability. This study evaluated 12 mAbs derived from three sets of variable regions, and identified the impact of IgG subclass on manufacturability and stability, which is important for therapeutic antibody development process.
Article
Medicine, Research & Experimental
Chunting Zhang, Steven T. Gossert, Jonathan Williams, Michael Little, Marilia Barros, Barton Dear, Bradley Falk, Ankit D. Kanthe, Robert Garmise, Luciano Mueller, Andrew Ilott, Anuji Abraham
Summary: By conducting direct experimental evidence, we have elucidated the mechanism by which excipients enhance protein stability through their binding affinity to monoclonal antibodies.
Article
Medicine, Research & Experimental
Riti Biswas, Ed Belouski, Kevin Graham, Michelle Hortter, Marissa Mock, Christine E. Tinberg, Alan J. Russell
Summary: We are transitioning into an era where therapeutic proteins are constructed using building block-like strategies, but there is no standardized protocol for discussing these formats. Existing nomenclatures sacrifice readability for precision, causing confusion and complexity in drug discovery. To overcome this challenge, VERITAS is introduced as a flexible classification and naming scheme for antibodies, adaptable to various therapeutic formats. VERITAS names are user-friendly and directly reflect the structure of a format, making them valuable in scientific discourse and drug development algorithms.
