Anti-DNA cell-penetrating autoantibodies have been extensively studied in autoimmune but not in normal sera. We investigated herein the presence and properties of cell-penetrating antibodies (CPAbs) in intravenous immunoglobulin (IVIg), a blood product of pooled normal human IgG. IVIg cell penetration was observed into various cell lines, as well as cells from several organs of mice injected intravenously with IVIg therapeutic dose. In all cell types examined in vitro and in vivo, intracellular IgG localized in the cytoplasm, in contrast to the nuclear accumulation of disease-related CPAbs. IVIg was found to rapidly enter cells via an energy-independent mode. The CPAb-fraction was isolated and found to be polyreactive to nuclear and cytoplasmic components; although it corresponded to ~2% of IVIg, it accounted for its inhibitory effect on splenocyte activation. Investigation of IVIg cell penetration capacity provides insight into its mechanisms of action and may account for some of its beneficial effects in numerous diseases.
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http://dx.doi.org/10.1038/cti.2015.18 | DOI Listing |
Angew Chem Int Ed Engl
January 2025
University at Buffalo - The State University of New York, Chemistry, 679 NSC, 14260-3000, Buffalo, UNITED STATES OF AMERICA.
Domain antibodies such as monobodies provide an attractive immunoglobin fold for evolving high-affinity protein binders targeting the intracellular proteins implicated in cell signalling. However, it remains a challenge to endow cell permeability to these small and versatile protein binders. Here, we report a streamlined approach combining orthogonal crosslinking afforded by a genetically encoded β-lactam-lysine (BeLaK) and genetic supercharging to generate cell-penetrating monobodies.
View Article and Find Full Text PDFACS Nano
January 2025
BK21 Program, Department of Applied Life Science, Konkuk University, Chungju 27478, Republic of Korea.
The tumor-specific efficacy of the most current anticancer therapeutic agents, including antibody-drug conjugates (ADCs), oligonucleotides, and photosensitizers, is constrained by limitations such as poor cell penetration and low drug delivery. In this study, we addressed these challenges by developing, a positively charged, amphiphilic Chlorin e6 (Ce6)-conjugated, cell-penetrating anti-PD-L1 peptide nanomedicine (CPPD1) with enhanced cell and tissue permeability. The CPPD1 molecule, a bioconjugate of a hydrophobic photosensitizer and strongly positively charged programmed cell death-ligand 1 (PD-L1) binding cell-penetrating peptide (CPP), is capable of self-assembling into nanoparticles with an average size of 199 nm in aqueous solution without the need for any carriers.
View Article and Find Full Text PDFMolecules
November 2024
Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Chemotherapies remain standard therapy for cancers but have limited efficacy and cause significant side effects, highlighting the need for targeted approaches. In the progression of cancer, tumors increase matrix metalloproteinase (MMP) activity. Leveraging and therapeutically redirecting tumor MMPs through activatable cell-penetrating peptide (ACPP) technology offers new approaches for tumor-selective drug delivery and for studying how drug payloads engage the tumor immune microenvironment.
View Article and Find Full Text PDFJ Thromb Haemost
November 2024
Department of Molecular Hematology, Sanquin Research and Landsteiner Laboratory, Amsterdam, The Netherlands. Electronic address:
Background: The main complication in hemophilia A treatment is the development of inhibitory antibodies against factor (F)VIII. Immune tolerance induction, the gold standard for eradicating anti-FVIII antibodies, is efficient in only 60% to 80% of cases. This underscores the need for more efficient induction of tolerance in patients with hemophilia A with FVIII inhibitors.
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