keyword
https://read.qxmd.com/read/38466436/molecular-probes-targeting-her2-pet-ct-and-their-application-in-advanced-breast-cancer
#21
REVIEW
Fang Gao, Fengxu Liu, Jun Wang, Junfang Bi, Luoping Zhai, Dong Li
PURPOSE: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer cases are among the most aggressive breast tumor subtypes. Accurately assessing HER2 expression status is vital to determining whether patients will benefit from targeted anti-HER2 treatment. HER2-targeted positron emission tomography (PET/CT) is noninvasive, enabling the real-time evaluation of breast cancer patient HER2 status with accuracy. METHODS: We summarize the research progress of PET/CT targeting HER2 in breast cancer, focusing on PET/CT molecular probes targeting HER2 and their clinical application in the management of advanced breast cancer...
March 11, 2024: Journal of Cancer Research and Clinical Oncology
https://read.qxmd.com/read/38466264/alternative-target-recognition-elements-for-chimeric-antigen-receptor-car-t-cells-beyond-standard-antibody-fragments
#22
JOURNAL ARTICLE
Matthew A Nix, Arun P Wiita
BACKGROUND AIMS: Chimeric antigen receptor T (CAR-T) cells are a remarkably efficacious, highly promising and rapidly evolving strategy in the field of immuno-oncology. The precision of these targeted cellular therapies is driven by the specificity of the antigen recognition element (the "binder") encoded in the CAR. This binder redirects these immune effector cells precisely toward a defined antigen on the surface of cancer cells, leading to T-cell receptor-independent tumor lysis. Currently, for tumor targeting most CAR-T cells are designed using single-chain variable fragments (scFvs) derived from murine or human immunoglobulins...
March 2, 2024: Cytotherapy
https://read.qxmd.com/read/38460144/quantitative-assessment-of-energetic-contributions-of-residues-in-a-sars-cov-2-viral-enzyme-nanobody-interface
#23
JOURNAL ARTICLE
Amit Kumar, Harish Vashisth
The highly conserved protease enzyme from SARS-CoV-2 (MPro ) is crucial for viral replication and is an attractive target for the design of novel inhibitory compounds. MPro is known to be conformationally flexible and has been stabilized in an extended conformation in a complex with a novel nanobody (NB2B4), which inhibits the dimerization of the enzyme via binding to an allosteric site. However, the energetic contributions of the nanobody residues stabilizing the MPro /nanobody interface remain unresolved...
March 9, 2024: Journal of Chemical Information and Modeling
https://read.qxmd.com/read/38459598/detection-of-her2-expression-using-99m-tc-nm-02-nanobody-in-patients-with-breast-cancer-a-non-randomized-non-blinded-clinical-trial
#24
JOURNAL ARTICLE
Lingzhou Zhao, Yan Xing, Changcun Liu, Shaofei Ma, Wenhua Huang, Zhen Cheng, Jinhua Zhao
BACKGROUND: 99m Tc radiolabeled nanobody NM-02 (99m Tc-NM-02) is a novel single photon emission computed tomography (SPECT) probe with a high affinity and specificity for human epidermal growth factor receptor 2 (HER2). In this study, a clinical imaging trial was conducted to investigate the relationship between 99m Tc-NM-02 uptake and HER2 expression in patients with breast cancer. METHODS: Thirty patients with pathologically confirmed breast cancer were recruited and imaged with both 99m Tc-NM-02 SPECT/computed tomography (CT) and 18 F-fluorodeoxyglucose (18 F-FDG) positron emission tomography (PET)/CT...
March 8, 2024: Breast Cancer Research: BCR
https://read.qxmd.com/read/38455046/using-protein-geometry-to-optimize-cytotoxicity-and-the-cytokine-window-of-a-ror1-specific-t-cell-engager
#25
JOURNAL ARTICLE
Xueyuan Zhou, Felix Klaus Geyer, Dominic Happel, Jeffrey Takimoto, Harald Kolmar, Brian Rabinovich
T cell engaging bispecific antibodies have shown clinical proof of concept for hematologic malignancies. Still, cytokine release syndrome, neurotoxicity, and on-target-off-tumor toxicity, especially in the solid tumor setting, represent major obstacles. Second generation TCEs have been described that decouple cytotoxicity from cytokine release by reducing the apparent binding affinity for CD3 and/or the TAA but the results of such engineering have generally led only to reduced maximum induction of cytokine release and often at the expense of maximum cytotoxicity...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38441773/preparation-of-chromobodies-for-the-detection-of-cell-surface-epitopes
#26
JOURNAL ARTICLE
Ugne Baronaite, Elise Cachat
Chromobodies are nanobodies genetically fused to fluorescent proteins, which were developed to visualize endogenous intracellular antigens. These versatile bioimaging nanotools can also be used to detect cell surface epitopes, and we describe here how we use them as an alternative to conjugated antibodies. This way, we routinely test the binding efficiency of nanobodies for their cognate cell surface antigens, before integrating them as sensing domains into complex synthetic receptor architectures.
2024: Methods in Molecular Biology
https://read.qxmd.com/read/38435828/a-bioengineered-anti-vegf-protein-with-high-affinity-and-high-concentration-for-intravitreal-treatment-of-wet-age-related-macular-degeneration
#27
JOURNAL ARTICLE
Chengnan Huang, Yuelin Wang, Jinliang Huang, Huiqin Liu, Zhidong Chen, Yang Jiang, Youxin Chen, Feng Qian
Intravitreal (IVT) injection of anti-vascular endothelial growth factor (anti-VEGF) has greatly improved the treatment of many retinal disorders, including wet age-related macular degeneration (wAMD), which is the third leading cause of blindness. However, frequent injections can be difficult for patients and may lead to various risks such as elevated intraocular pressure, infection, and retinal detachment. To address this issue, researchers have found that IVT injection of anti-VEGF proteins at their maximally viable concentration and dose can be an effective strategy...
March 2024: Bioengineering & Translational Medicine
https://read.qxmd.com/read/38428724/improved-antitumor-effects-elicited-by-an-oncolytic-hsv-1-expressing-a-novel-b7h3nb-cd3-bsab
#28
JOURNAL ARTICLE
Zongliang Zhang, Nian Yang, Huaqing Lu, Yongdong Chen, Long Xu, Zeng Wang, Qizhong Lu, Kunhong Zhong, Zhixiong Zhu, Guoqing Wang, Hexian Li, Meijun Zheng, Weiwei Zhang, Hui Yang, Xingchen Peng, Liangxue Zhou, Aiping Tong
Oncolytic viruses have emerged as a promising modality for cancer treatment due to their unique abilities to directly destroy tumor cells and modulate the tumor microenvironment. Bispecific T-cell engagers (BsAbs) have been developed to activate and redirect cytotoxic T lymphocytes, enhancing the antitumor response. To take advantage of the specific infection capacity and carrying ability of exogenous genes, we generated a recombinant herpes simplex virus type 1 (HSV-1), HSV-1dko -B7H3nb/CD3 or HSV-1dko -B7H3nb/mCD3, carrying a B7H3nb/CD3 or B7H3nb/mCD3 BsAb that replicates and expresses BsAb in tumor cells in vitro and in vivo...
February 28, 2024: Cancer Letters
https://read.qxmd.com/read/38423996/epitope-identification-of-an-mglu5-receptor-nanobody-using-physics-based-molecular-modeling-and-deep-learning-techniques
#29
JOURNAL ARTICLE
Floriane Eshak, Léo Pion, Pauline Scholler, Damien Nevoltris, Patrick Chames, Philippe Rondard, Jean-Philippe Pin, Francine C Acher, Anne Goupil-Lamy
The world has witnessed a revolution in therapeutics with the development of biological medicines such as antibodies and antibody fragments, notably nanobodies. These nanobodies possess unique characteristics including high specificity and modulatory activity, making them promising candidates for therapeutic applications. Identifying their binding mode is essential for their development. Experimental structural techniques are effective to get such information, but they are expensive and time-consuming. Here, we propose a computational approach, aiming to identify the epitope of a nanobody that acts as an agonist and a positive allosteric modulator at the rat metabotropic glutamate receptor 5...
February 29, 2024: Journal of Chemical Information and Modeling
https://read.qxmd.com/read/38417327/research-note-clostridium-perfringens-netb-and-cnaa-neutralizing-nanobodies-in-feed-reduce-the-incidence-of-poultry-necrotic-enteritis
#30
JOURNAL ARTICLE
Slade A Loutet, Sylvia Cheung, Sarah Zaytsoff, Charles Hofacre, Matthew K Jones, Filip Van Petegem, Hamlet Abnousi
Necrotic enteritis is a devastating disease to poultry caused by the bacterium Clostridium perfringens. As a novel approach to combating poultry necrotic enteritis, we identified and characterized several hundred single domain antibody fragments (or nanobodies) capable of binding either the NetB toxin or the collagen-binding adhesin (CnaA) of C. perfringens. Many of the nanobodies could neutralize the in vitro functions of NetB or CnaA with inhibitory concentrations in the nanomolar range. The nanobodies were also screened for proteolytic stability in an extract derived from gastrointestinal tract fluids of chickens...
February 22, 2024: Poultry Science
https://read.qxmd.com/read/38413606/q586b2-is-a-crucial-virulence-factor-during-the-early-stages-of-trypanosoma-brucei-infection-that-is-conserved-amongst-trypanosomatids
#31
JOURNAL ARTICLE
Benoit Stijlemans, Patrick De Baetselier, Inge Van Molle, Laurence Lecordier, Erika Hendrickx, Ema Romão, Cécile Vincke, Wendy Baetens, Steve Schoonooghe, Gholamreza Hassanzadeh-Ghassabeh, Hannelie Korf, Marie Wallays, Joar E Pinto Torres, David Perez-Morga, Lea Brys, Oscar Campetella, María S Leguizamón, Mathieu Claes, Sarah Hendrickx, Dorien Mabille, Guy Caljon, Han Remaut, Kim Roelants, Stefan Magez, Jo A Van Ginderachter, Carl De Trez
Human African trypanosomiasis or sleeping sickness, caused by the protozoan parasite Trypanosoma brucei, is characterized by the manipulation of the host's immune response to ensure parasite invasion and persistence. Uncovering key molecules that support parasite establishment is a prerequisite to interfere with this process. We identified Q586B2 as a T. brucei protein that induces IL-10 in myeloid cells, which promotes parasite infection invasiveness. Q586B2 is expressed during all T. brucei life stages and is conserved in all Trypanosomatidae...
February 27, 2024: Nature Communications
https://read.qxmd.com/read/38408177/polyvalent-nanobody-structure-designed-for-boosting-sars-cov-2-inhibition
#32
JOURNAL ARTICLE
Tingjie Song, Laura Cooper, Jazmin Galván Achi, Xiaojing Wang, Abhisek Dwivedy, Lijun Rong, Xing Wang
Coronavirus transmission and mutations have brought intensive challenges on pandemic control and disease treatment. Developing robust and versatile antiviral drugs for viral neutralization is highly desired. Here, we created a new polyvalent nanobody (Nb) structure that shows the effective inhibition of SARS-CoV-2 infections. Our polyvalent Nb structure, called "PNS", is achieved by first conjugating single-stranded DNA (ssDNA) and the receptor-binding domain (RBD)-targeting Nb with retained binding ability to SARS-CoV-2 spike protein and then coalescing the ssDNA-Nb conjugates around a gold nanoparticle (AuNP) via DNA hybridization with a desired Nb density that offers spatial pattern-matching with that of the Nb binding sites on the trimeric spike...
February 26, 2024: Journal of the American Chemical Society
https://read.qxmd.com/read/38405763/degron-based-bioprotacs-for-controlling-signaling-in-car-t-cells
#33
Matthew S Kim, Hersh K Bhargava, Gavin E Shavey, Wendell A Lim, Hana El-Samad, Andrew H Ng
Chimeric antigen receptor (CAR) T cells have made a tremendous impact in the clinic, but potent signaling through the CAR can be detrimental to treatment safety and efficacy. The use of protein degradation to control CAR signaling can address these issues in pre-clinical models. Existing strategies for regulating CAR stability rely on small molecules to induce systemic degradation. In contrast to small molecule regulation, genetic circuits offer a more precise method to control CAR signaling in an autonomous, cell-by-cell fashion...
February 17, 2024: bioRxiv
https://read.qxmd.com/read/38404205/streptavidin-biotin-system-mediated-immobilization-of-a-bivalent-nanobody-onto-magnetosomes-for-separation-and-analysis-of-3-phenoxybenzoic-acid-in-urine
#34
JOURNAL ARTICLE
Fang Tang, Yating Wang, Di Wang, Yayun Yang, Jiashu Chang, Huabo Sun, Shaopeng Gu, Jinxin He
The compound 3-phenoxybenzoic acid (3-PBA) is frequently utilized as a biomarker to detect exposure to various pyrethroids. In this study, a bivalent nanobody (Nb2) specifically targeting 3-PBA was biotinylated and immobilized onto streptavidin (SA)-modified bacterial magnetic nanoparticles (BMPs), resulting in the formation of BMP-SA-Biotin-Nb2 complexes. These complexes demonstrated remarkable stability when exposed to strongly acidic solutions (4 M HCl), methanol (80%), and high ionic strength (1.37 M NaCl)...
February 26, 2024: Analytical Methods: Advancing Methods and Applications
https://read.qxmd.com/read/38404052/tracing-endogenous-proteins-in-living-cells-through-electrotransfer-of-mrna-encoding-chromobodies
#35
JOURNAL ARTICLE
Théo Juncker, Ludovic Richert, Murielle Masson, Guy Zuber, Bruno Chatton, Mariel Donzeau
Chromobodies made of nanobodies fused to fluorescent proteins are powerful tools for targeting and tracing intracellular proteins in living cells. Typically, this is achieved by transfecting plasmids encoding the chromobodies. However, an excess of unbound chromobody relative to the endogenous antigen can result in high background fluorescence in live cell imaging. Here, we overcome this problem by using mRNA encoding chromobodies. Our approach allows one to precisely control the amount of chromobody expressed inside the cell by adjusting the amount of transfected mRNA...
February 2024: Biotechnology Journal
https://read.qxmd.com/read/38400113/serial-llama-immunization-with-various-sars-cov-2-rbd-variants-induces-broad-spectrum-virus-neutralizing-nanobodies
#36
JOURNAL ARTICLE
Pavel P Solodkov, Alexander M Najakshin, Nikolai A Chikaev, Sergey V Kulemzin, Ludmila V Mechetina, Konstantin O Baranov, Sergey V Guselnikov, Andrey A Gorchakov, Tatyana N Belovezhets, Anton N Chikaev, Olga Y Volkova, Alexander G Markhaev, Yulia V Kononova, Alexander Y Alekseev, Marina A Gulyaeva, Alexander M Shestopalov, Alexander V Taranin
The emergence of SARS-CoV-2 mutant variants has posed a significant challenge to both the prevention and treatment of COVID-19 with anti-coronaviral neutralizing antibodies. The latest viral variants demonstrate pronounced resistance to the vast majority of human monoclonal antibodies raised against the ancestral Wuhan variant. Less is known about the susceptibility of the evolved virus to camelid nanobodies developed at the start of the pandemic. In this study, we compared nanobody repertoires raised in the same llama after immunization with Wuhan's RBD variant and after subsequent serial immunization with a variety of RBD variants, including that of SARS-CoV-1...
January 26, 2024: Vaccines
https://read.qxmd.com/read/38399961/sars-cov-2-specific-nanobodies-neutralize-different-variants-of-concern-and-reduce-virus-load-in-the-brain-of-h-ace2-transgenic-mice
#37
JOURNAL ARTICLE
María Florencia Pavan, Marina Bok, Rafael Betanzos San Juan, Juan Pablo Malito, Gisela Ariana Marcoppido, Diego Rafael Franco, Daniela Ayelen Militelo, Juan Manuel Schammas, Sara Elizabeth Bari, William Stone, Krisangel López, Danielle LaBrie Porier, John Anthony Muller, Albert Jonathan Auguste, Lijuan Yuan, Andrés Wigdorovitz, Viviana Gladys Parreño, Lorena Itat Ibañez
Since the beginning of the COVID-19 pandemic, there has been a significant need to develop antivirals and vaccines to combat the disease. In this work, we developed llama-derived nanobodies (Nbs) directed against the receptor binding domain (RBD) and other domains of the Spike (S) protein of SARS-CoV-2. Most of the Nbs with neutralizing properties were directed to RBD and were able to block S-2P/ACE2 interaction. Three neutralizing Nbs recognized the N-terminal domain (NTD) of the S-2P protein. Intranasal administration of Nbs induced protection ranging from 40% to 80% after challenge with the WA1/2020 strain in k18-hACE2 transgenic mice...
January 25, 2024: Viruses
https://read.qxmd.com/read/38396724/anti-idiotypic-nanobodies-mimicking-an-epitope-of-the-needle-protein-of-the-chlamydial-type-iii-secretion-system-for-targeted-immune-stimulation
#38
JOURNAL ARTICLE
Ekaterina A Koroleva, Oksana S Goryainova, Tatiana I Ivanova, Marina V Rutovskaya, Naylia A Zigangirova, Sergei V Tillib
The development of new approaches and drugs for effective control of the chronic and complicated forms of urogenital chlamydia caused by Chlamydia trachomatis , which is suspected to be one of the main causes of infertility in both women and men, is an urgent task. We used the technology of single-domain antibody (nanobody) generation both for the production of targeting anti-chlamydia molecules and for the subsequent acquisition of anti-idiotypic nanobodies (ai-Nbs) mimicking the structure of a given epitope of the pathogen (the epitope of the Chlamydial Type III Secretion System Needle Protein)...
February 7, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38395797/noninvasive-evaluation-of-tumoral-pd-l1-using-a-novel-99m-tc-labeled-nanobody-tracer-with-rapid-renal-clearance
#39
JOURNAL ARTICLE
Biao Hu, Xiaopan Ma, Linqing Shi, Tianyu Liu, Liqiang Li, Meinan Yao, Chenzhen Li, Bing Jia
The expression level of PD-L1 in tumor tissue is considered one of the effective biomarkers to guide PD-1/PD-L1 therapy. Quantifying whole-body PD-L1 expression by SPECT imaging may help in selecting patients that potentially respond to PD-1/PD-L1 therapy. Nanobody is the smallest antibody fragment with antigen-binding ability that is well suited for radionuclide imaging. Nevertheless, high retention of radioactivity in the kidney may limit its clinical translation. The present study aimed to screen, design, and prepare a nanobody-based SPECT probe with rapid renal clearance to evaluate the PD-L1 expression level in vivo noninvasively...
February 23, 2024: Molecular Pharmaceutics
https://read.qxmd.com/read/38388771/secretion-of-the-fungal-toxin-candidalysin-is-dependent-on-conserved-precursor-peptide-sequences
#40
JOURNAL ARTICLE
Rita Müller, Annika König, Sabrina Groth, Robert Zarnowski, Corissa Visser, Tom Handrianz, Corinne Maufrais, Thomas Krüger, Maximilian Himmel, Sejeong Lee, Emily L Priest, Deniz Yildirim, Jonathan P Richardson, Matthew G Blango, Marie-Elisabeth Bougnoux, Olaf Kniemeyer, Christophe d'Enfert, Axel A Brakhage, David R Andes, Verena Trümper, Christian Nehls, Lydia Kasper, Selene Mogavero, Thomas Gutsmann, Julian R Naglik, Stefanie Allert, Bernhard Hube
The opportunistic fungal pathogen Candida albicans damages host cells via its peptide toxin, candidalysin. Before secretion, candidalysin is embedded in a precursor protein, Ece1, which consists of a signal peptide, the precursor of candidalysin and seven non-candidalysin Ece1 peptides (NCEPs), and is found to be conserved in clinical isolates. Here we show that the Ece1 polyprotein does not resemble the usual precursor structure of peptide toxins. C. albicans cells are not susceptible to their own toxin, and single NCEPs adjacent to candidalysin are sufficient to prevent host cell toxicity...
February 22, 2024: Nature Microbiology
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