Despite the immense clinical success of the antibody therapeutics that neutralize programmed death receptor ligand 1 (PD-L1) and thus resurrect T cell antitumor activity, the patient response rates remain low. In this issue of Cell Chemical Biology, Ludwig et al. reveal novel topologies of multiparatopic antibodies that mediate potent PD-L1 downregulation.
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Plug-and-play nucleic acid-mediated multimerization of biparatopic nanobodies for molecular imaging.
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Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000 Aarhus C, Denmark.
In cancer molecular imaging, selecting binders with high specificity and affinity for biomarkers is paramount for achieving high-contrast imaging within clinical time frames. Nanobodies have emerged as potent candidates, surpassing antibodies in pre-clinical imaging due to their convenient production, rapid renal clearance, and deeper tissue penetration. Multimerization of nanobodies is a popular strategy to enhance their affinity and pharmacokinetics; however, traditional methods are laborious and may yield heterogeneous products.
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Institute of Molecular Biotechnology, Department of Biotechnology, BOKU University, Vienna, Austria; acib GmbH (Austrian Centre of Industrial Biotechnology), Graz, Austria.
Despite the immense clinical success of the antibody therapeutics that neutralize programmed death receptor ligand 1 (PD-L1) and thus resurrect T cell antitumor activity, the patient response rates remain low. In this issue of Cell Chemical Biology, Ludwig et al. reveal novel topologies of multiparatopic antibodies that mediate potent PD-L1 downregulation.
View Article and Find Full Text PDFMultiparatopic antibodies induce targeted downregulation of programmed death-ligand 1.
Cell Chem Biol
May 2024
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. Electronic address:
Programmed death-ligand 1 (PD-L1) drives inhibition of antigen-specific T cell responses through engagement of its receptor programmed death-1 (PD-1) on activated T cells. Overexpression of these immune checkpoint proteins in the tumor microenvironment has motivated the design of targeted antibodies that disrupt this interaction. Despite clinical success of these antibodies, response rates remain low, necessitating novel approaches to enhance performance.
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Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; email:
Antibody-based therapeutics constitute a rapidly growing class of pharmaceutical compounds. However, monoclonal antibodies, which specifically engage only one target, often lack the mechanistic intricacy to treat complex diseases. To expand the utility of antibody therapies, significant efforts have been invested in designing multispecific antibodies, which engage multiple targets using a single molecule.
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