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A whole-body imaging technique for tumor-specific diagnostics and screening of B7-H3-targeted therapies.
J Clin Invest
January 2025
Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China.
Background: B7-H3 or CD276 is notably overexpressed in various malignant tumor cells in humans, with extremely high expression rates. The development of a radiotracer that targets B7-H3 may provide a universal tumor-specific imaging agent and allow the noninvasive assessment of the whole-body distribution of B7-H3-expressing lesions.
Methods: We enhanced and optimized the structure of an affibody (ABY) that targets B7-H3 to create the radiolabeled radiotracer [68Ga]Ga-B7H3-BCH, and then, we conducted both foundational experiments and clinical translational studies.
ANKRD11 binding to cohesin suggests a connection between KBG syndrome and Cornelia de Lange syndrome.
Proc Natl Acad Sci U S A
January 2025
Shenzhen Key Laboratory of Biomolecular Assembling and Regulation, Department of Neuroscience, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
Ankyrin Repeat Domain-containing Protein 11 () is a causative gene for KBG syndrome, a significant risk factor for Cornelia de Lange syndrome (CdLS), and a highly confident autism spectrum disorder gene. Mutations of lead to developmental abnormalities in multiple organs/tissues including the brain, craniofacial and skeletal bones, and tooth structures with unknown mechanism(s). Here, we find that ANKRD11, via a short peptide fragment in its N-terminal region, binds to the cohesin complex with a high affinity, implicating why mutation can cause CdLS.
View Article and Find Full Text PDFPro-angiogenic VEGF inhibition by cadaverine and hydrocinnamic acid metabolites: impairment of periodontal regeneration due to periodontal inflammation.
Minerva Dent Oral Sci
January 2025
Department of Biomedical Sciences, Dentistry and Morphological and Functional Imaging, University of Messina, Messina, Italy.
Background: Cadaverine and hydrocinnamic acid are frequent metabolites in inflamed periodontal areas. Their role as a metabolite for plant growth inhibition has been established, but their relevance in humans has yet to be determined. Moreover, Vascular endothelial growth factor (VGEF) is a consistent growth factor in neo-angiogenesis in periodontal regeneration.
View Article and Find Full Text PDFEngineering of a lysosomal-targeted GAA enzyme.
Protein Eng Des Sel
January 2025
Pfizer Rare Disease Research Unit, 610 Main Street, Cambridge, MA 02139, United States.
Pompe disease is a tissue glycogen disorder caused by genetic insufficiency of the GAA enzyme. GAA enzyme replacement therapies for Pompe disease have been limited by poor lysosomal trafficking of the recombinant GAA molecule through the native mannose-6-phosphate-mediated pathway. Here, we describe the successful rational engineering of a chimeric GAA enzyme that utilizes the binding affinity of a modified IGF-II moiety to its native receptor to bypass the mannose-6-phosphate-mediated lysosomal trafficking pathway, conferring a significant increase in cellular uptake of the GAA enzyme.
View Article and Find Full Text PDFA Strategy for Simultaneous Engineering of Interspecies Cross-Reactivity, Thermostability, and Expression of a Bispecific 5T4 x CD3 DART Molecule for Treatment of Solid Tumors.
Antibodies (Basel)
January 2025
MacroGenics Inc., Rockville, MD 20850, USA.
Bispecific antibodies represent a promising class of biologics for cancer treatment. However, their dual specificity and complex structure pose challenges in the engineering process, often resulting in molecules with good functional but poor physicochemical properties. To overcome limitations in the properties of an anti-5T4 x anti-CD3 (α5T4 x αCD3) DART molecule, a phage-display method was developed, which succeeded in simultaneously engineering cross-reactivity to the cynomolgus 5T4 ortholog, improving thermostability and the elevating expression level.
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