Article
Oncology
Zhijie Zhang, Chang Liu, Muhan Wang, Rongcheng Sun, Zhe Yang, Zhen Hua, Yushuang Wu, Mengting Wu, Hang Wang, Wen Qiu, Hongping Yin, Meijia Yang
Summary: In this study, it was found that targeting EDB-fibronectin by rTCR-CAR T cells can overcome the suppressive tumor microenvironment and effectively suppress tumor growth.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Oncology
Sophia Stock, Mohamed-Reda Benmebarek, Anna-Kristina Kluever, Diana Darowski, Christian Jost, Kay-Gunnar Stubenrauch, Joerg Benz, Anne Freimoser-Grundschober, Ekkehard Moessner, Pablo Umana, Marion Subklewe, Stefan Endres, Christian Klein, Sebastian Kobold
Summary: This study developed a P329G-directed CAR T cell that can selectively bind with specific mutated antibodies, demonstrating significant in vitro and in vivo effector functions in different types of solid tumor models. This opens up possibilities for further clinical translation.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Multidisciplinary Sciences
Jake Burton, Jesus A. Siller-Farfan, Johannes Pettmann, Benjamin Salzer, Mikhail Kutuzov, P. Anton van der Merwe, Omer Dushek
Summary: Chimeric antigen receptors (CARs) have lower sensitivity to antigens presented on antigen-presenting cells (APCs) compared to T cell receptors (TCR), but nearly identical sensitivity to purified protein antigens. Engaging CD2 or LFA-1 can significantly improve TCR sensitivity, but has minimal effect on CAR sensitivity. Fusion of CAR variable domains to the TCR CD3 epsilon subunit (TRuC) or exchanging TCR alpha beta variable domains for those of the CAR (STAR or HIT) can partially or fully restore antigen sensitivity, respectively, by enhancing their ability to exploit CD2 and LFA-1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Thaddaeus Mutugi Nthiga, Birendra Kumar Shrestha, Jack-Ansgar Bruun, Kenneth Bowitz Larsen, Trond Lamark, Terje Johansen
Summary: The Golgi complex plays a crucial role in the processing and trafficking of proteins and lipids, with its turnover regulated to meet cellular demands. This study uncovers a mechanism where CALCOCO1 interacts with ZDHHC17 to facilitate Golgi degradation through autophagy, influencing Golgi size and morphology during starvation.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Oncology
Jinrong Yang, Weilin Zhou, Dan Li, Ting Niu, Wei Wang
Summary: This article summarizes the application and research progress of BCMA-targeting CAR T cell therapy in the treatment of multiple myeloma, as well as measures to improve efficacy and safety.
Review
Oncology
Kai Dai, Yin Wu, Sha She, Qian Zhang
Summary: CAR-NK cells, as a revolutionary cellular immunotherapy, have the potential to kill hepatocellular carcinoma cells independently of major histocompatibility complex matching, and recent advances in genetic engineering have been made, but challenges still exist.
WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY
(2021)
Article
Oncology
Michael Winkelmann, Viktoria Blumenberg, Kai Rejeski, Christina Quell, Veit Buecklein, Maria Ingenerf, Marcus Unterrainer, Christian Schmidt, Franziska J. Dekorsy, Peter Bartenstein, Jens Ricke, Michael von Bergwelt-Baildon, Marion Subklewe, Wolfgang G. Kunz
Summary: This study aimed to improve the prediction of overall survival in patients with refractory or relapsed lymphoma by including the tumor growth rate and its change in imaging. The results showed that using these factors in combination with the Lugano criteria can better predict the overall survival of patients with progressive disease.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Review
Biochemistry & Molecular Biology
Katarzyna M. Terlikowska, Bozena Dobrzycka, Slawomir J. Terlikowski
Summary: The advancement in our understanding of tumor biology has led to the development of targeted molecular therapies, such as CARs, which show potential in treating ovarian cancer. identification. CARs targeting overexpressed molecules in tumor cells causes high toxicity and reduces tumor burden with minimal side effects, inhibiting disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xiaona Wang, Fengcheng Li, Wenqi Qiu, Binbin Xu, Yanlin Li, Xichen Lian, Hongyan Yu, Zhao Zhang, Jianxin Wang, Zhaorong Li, Weiwei Xue, Feng Zhu
Summary: The SYNBIP database provides comprehensive information on thousands of SBPs, illustrating their scaffolds, biophysical and functional properties, binding targets and applications, as well as enabling similarity search. This database serves as a valuable resource for future development of novel SBPs through experimental protein engineering and in-silico studies. The SYNBIP database is accessible without login requirement at both official and mirror sites.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
P. Connor Johnson, Caron Jacobson, Alisha Yi, Mahmoud R. Gaballa, Nora Horick, Dustin J. Rabideau, Kevin Lindell, Gabriel D. DePinho, Areej R. El-Jawahri, Matthew J. Frigault
Summary: A retrospective analysis of 235 patients receiving CAR T-cell therapy found that bridging therapy use was not associated with differences in overall response, complete response rate, or progression-free survival, but was associated with worse overall survival. Additional poor prognostic factors may contribute to this association, highlighting the need for innovative bridging therapy regimens for these patients.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Rui Zheng, Yuankun Chen, Yiting Zhang, Sixin Liang, Xiaojuan Zhao, Yiyi Wang, Pengju Wang, Ruotong Meng, Angang Yang, Bo Yan
Summary: Our study explores the effect of low-affinity CARs using humanized scFvs on the function of CAR-T cells. We find that moderately reducing the affinity of CARs can maintain anti-tumor efficacy and improve the safety of CAR therapy both in vitro and in vivo. In addition, T cells expressing the VL domain only antibody show long-lasting tumor elimination capability and lower cytokine levels.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Marta Ripamonti, Nicolas Liaudet, Latifeh Azizi, Daniel Bouvard, Vesa P. Hytonen, Bernhard Wehrle-Haller
Summary: The study provides insights into the molecular organization of beta 3 integrin-FAs, showing the specific contributions of individual Paxillin LIM domains in targeting and maintaining the structural integrity of focal adhesions (FAs). Ripamonti et al. demonstrate the importance of mechanical coupling of paxillin in the FA to the plasma membrane or integrin for FA stability and integrin-talin linkage.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jiao Wang, Sandra Toregrosa-Allen, Bennett D. Elzey, Sagar Utturkar, Nadia Atallah Lanman, Victor Bernal-Crespo, Matthew M. Behymer, Gregory T. Knipp, Yeonhee Yun, Michael C. Veronesi, Anthony L. Sinn, Karen E. Pollok, Randy R. Brutkiewicz, Kathryn S. Nevel, Sandro Matosevic
Summary: This study demonstrates a promising strategy utilizing genetically engineered human NK cells as a multifunctional immunotherapy to target multiple mechanisms of GBM progression simultaneously, including addressing antigen escape, immunometabolic reprogramming, and immune cell homing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Lin Niu, Yu-jie Lu, Xing-wang Zu, Wen Yang, Fu-kui Shen, Yan-yan Xu, Min Jiang, Yang Xie, Su-yun Li, Jie Gao, Gang Bai
Summary: This study focuses on the role of TRPV4 in fibrosis in chronic obstructive pulmonary disease (COPD) and investigates the therapeutic effect and mechanism of action of magnolol (MAG) on TRPV4. The results demonstrate that MAG disrupts the binding between phosphatidylinositol 3 kinase and TRPV4 by targeting its ankyrin repeat domain (ARD), inhibiting the membrane distribution and channel activity of TRPV4, consequently alleviating fibrosis in COPD.
PHYTOTHERAPY RESEARCH
(2023)
Article
Oncology
Jonathan E. Brammer, Zachary Braunstein, Aashish Katapadi, Kyle Porter, Michael Biersmith, Avirup Guha, Sumithira Vasu, Vedat O. Yildiz, Sakima A. Smith, Benjamin Buck, Devin Haddad, Richard Gumina, Basem M. William, Sam Penza, Ayman Saad, Nathan Denlinger, Ajay Vallakati, Ragavendra Baliga, Raymond Benza, Philip Binkley, Lai Wei, Mason Mocarski, Steven M. Devine, Samantha Jaglowski, Daniel Addison
Summary: Moderate toxicity such as grade 2 CRS after CAR-T infusion in adult lymphoma patients may be associated with favorable clinical outcomes. Further studies are needed to confirm these findings.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Review
Biochemistry & Molecular Biology
Florian J. Gisdon, Josef P. Kynast, Merve Ayyildiz, Anna V. Hine, Andreas Pluckthun, Birte Hoecker
Summary: Current biomedical research and diagnostics rely heavily on detection agents for specific identification and quantification of protein molecules. Commercial reagent antibodies, however, lack specificity or fail to recognize their target. Hence, there is a need for synthetic alternatives developed through multidisciplinary approaches integrating experimental protein engineering with computational modeling.
BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Jendrik Schoppe, Janosch Ehrenmann, Yann Waltenspuhl, Andreas Pluckthun
Summary: Structural studies of G-protein-coupled receptors (GPCRs) are often limited by difficulties in obtaining well-diffracting crystals. This protocol describes how to generate and screen for mutants with better thermal stability that is indicative for successful crystallization in lipidic cubic phase.
Correction
Multidisciplinary Sciences
Shinya Matsuda, Jonas V. Schaefer, Yusuke Mii, Yutaro Hori, Dimitri Bieli, Masanori Taira, Andreas Pluckthun, Markus Affolter
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Mattia Deluigi, Lena Morstein, Matthias Schuster, Christoph Klenk, Lisa Merklinger, Riley R. Cridge, Lazarus A. de Zhang, Alexander Klipp, Santiago Vacca, Tasneem M. Vaid, Peer R. E. Mittl, Pascal Egloff, Stefanie A. Eberle, Oliver Zerbe, David K. Chalmers, Daniel J. Scott, Andreas Pluckthun
Summary: This study reports the X-ray structure of the alpha(1B)-adrenergic G protein-coupled receptor bound to an inverse agonist and identifies key determinants of subtype-selective ligand binding. This finding is important for the design of aminergic drugs with fewer side-effects.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Sofia S. Guimaraes Koch, Robin Thorpe, Nana Kawasaki, Marie-Paule Lefranc, Sarel Malan, Andrew C. R. Martin, Gilles Mignot, Andreas Pluckthun, Menico Rizzi, Stephanie Shubat, Karin Weisser, Raffaella Balocco
Summary: Appropriate nomenclature is crucial for pharmaceutical substances and their development. The WHO INN Programme has revised the naming system for antibody-based drugs and introduced new stems to address the challenge of distinguishing names.
Article
Multidisciplinary Sciences
Jie Shi, Kristine Hauschulte, Ivan Mikicic, Srijana Maharjan, Valerie Arz, Tina Strauch, Jan B. Heidelberger, Jonas Schaefer, Birgit Dreier, Andreas Plueckthun, Petra Beli, Helle D. Ulrich, Hans-Peter Wollscheid
Summary: The study investigates the role of actin and associated molecules in the nucleus, focusing on the actin-based motor myosin VI in protecting stalled replication forks. The actin cytoskeleton is important for cellular structure and plasticity, but the abundance and function of filamentous actin in the nucleus are still debated.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Christoph Klenk, Maria Scrivens, Anina Niederer, Shuying Shi, Loretta Mueller, Elaine Gersz, Maurice Zauderer, Ernest S. Smith, Ralf Strohner, Andreas Pluckthun
Summary: The authors developed a method to alter the biophysical and functional properties of G protein-coupled receptors through directed evolution in mammalian cells. They evolved neurotensin receptor 1 for high stability and expression and demonstrated that receptors with complex molecular architectures and large ligands can also be evolved. Importantly, their approach allows for the evolution of functional receptor properties in the presence of the mammalian signaling environment, resulting in receptor variants with increased allosteric coupling.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Marine Blanc, Clara Lettl, Jeremy Guerin, Anais Vieille, Sven Furler, Sylvie Briand-Schumacher, Birgit Dreier, Celia Berge, Andreas Pluckthun, Sandrine Vadon-Le Goff, Remi Fronzes, Patricia Rousselle, Wolfgang Fischer, Laurent Terradot
Summary: The study focuses on Helicobacter pylori, a bacterial pathogen that injects the oncoprotein CagA into gastric cells using a type IV secretion system (cagT4SS). The research shows that CagI, a protein present on the surface of the bacterium, is crucial for the formation of the pilus that facilitates CagA delivery. DARPins targeting CagI are identified as potent inhibitors of the cagT4SS, which is a major risk factor for gastric cancer development.
Article
Biology
Rajib Schubert, Taegeun Bae, Branko Simic, Sheena N. Smith, Seong-Ho Park, Gabriela Nagy-Davidescu, Viviana Gradinaru, Andreas Pluckthun, Junho K. Hur
Summary: Tissue clearing combined with deep imaging is a powerful tool for expanding classical histological techniques. However, imaging highly melanin-rich tissues remains challenging. To address this, researchers developed a CRISPR-based gene editing method called CRISPR-Clear, which can be incorporated into existing tissue-clearing workflows. The method was successfully applied to melanoma tumors, allowing detailed characterization through staining and imaging techniques.
COMMUNICATIONS BIOLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ruben D. Houvast, Nada Badr, Taryn March, Lysanne D. A. N. de Muynck, Vincent Q. Sier, Timo Schomann, Shadhvi Bhairosingh, Victor M. Baart, Judith A. H. M. Peeters, Gerard J. P. van Westen, Andreas Plueckthun, Jacobus Burggraaf, Peter J. K. Kuppen, Alexander L. Vahrmeijer, Cornelis F. M. Sier
Summary: This study evaluated the preclinical potential of EpCAM-binding DARPins for NIRF and PA imaging of cancer, demonstrating clear tumor delineation in vivo.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Biochemistry & Molecular Biology
Sarah Klinnert, Corinne D. Schenkel, Patrick C. Freitag, Huldrych F. Guenthard, Andreas Plueckthun, Karin J. Metzner
Summary: This study uses gene therapy to target and eliminate cells infected with HIV-1 by activating latent virus and killing the cells. This targeted gene therapy approach has the potential to effectively and safely eliminate infected cells.
Article
Immunology
Liridona Maliqi, Nikolas Friedrich, Matthias Glogl, Stefan Schmutz, Daniel Schmidt, Peter Rusert, Merle Schanz, Maryam Zaheri, Chloe Pasin, Cyrille Niklaus, Caio Foulkes, Thomas Reinberg, Birgit Dreier, Irene Abela, David Peterhoff, Alexandra Hauser, Roger D. Kouyos, Huldrych F. Guenthard, Marit J. van Gils, Rogier W. Sanders, Ralf Wagner, Andreas Plueckthun, Alexandra Trkola
Summary: Understanding the balance between epitope shielding and accessibility on HIV-1 envelope trimers is crucial for selecting immunogens for bnAb-based vaccines. This study introduces a strategy using synthetic DARPin libraries to investigate the antigenic properties of Env immunogens. The in vitro screening tool, DANA, can provide relevant information of antigenic features of Env immunogens. The findings demonstrate that stronger trimer stabilization leads to the selection of highly mutated DARPins, mirroring observations made for bnAbs. By mimicking immunization regimens, DANA can be used to select immunogen combinations that favor trimer-reactive binders.
Article
Biochemistry & Molecular Biology
Melanie Gut, Birgit Dreier, Sven Furler, Jens Sobek, Andreas Pluckthun, Jason P. Holland
Summary: Late-stage prostate cancer often becomes resistant to standard chemotherapy and transforms into a hormone-resistant, drug-resistant, and incurable disease. Developing non-invasive tools to detect biochemical changes that indicate drug efficacy and identify drug resistance could have significant implications in managing individual patients' treatment plans. In this study, new Designed Ankyrin Repeat Proteins (DARPins) with high affinity for prostate-specific antigen (PSA) were selected using ribosome display and in vitro screening tools. These PSAbinding DARPins showed nanomolar affinity for PSA and could be radiolabeled for potential use in imaging-based monitoring of androgen receptor (AR)-targeted therapies.
RSC CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christian Baumann, Wan-Chin Chiang, Renato Valsecchi, Simon Jurt, Mattia Deluigi, Matthias Schuster, Karl Johan Rosengren, Andreas Pluckthun, Oliver Zerbe
Summary: This study investigates the rapid side-chain dynamics of an alpha(1B)-adrenergic receptor using methyl relaxation. The results show that the overall side-chain dynamics of the receptor are similar in the presence of different ligands. However, the allosteric ligand increases the flexibility of certain key residues, suggesting differences in the mechanisms for receptor activation. These findings demonstrate the feasibility of studying receptor-wide side-chain dynamics in GPCRs to gain functional insights.
Meeting Abstract
Biotechnology & Applied Microbiology
Sebastian Schellhorn, Dominik Bruecher, Natascha A. Wolff, Katrin Schroeer, Erwan Sallard, Kemal Mese, Wenli Zhang, Eric Ehrke-Schulz, Frank Thevenod, Andreas Plueckthun, Anja Ehrhardt