scholarly journals Increased serum clearance of oligomannose species present on a human IgG1 molecule

mAbs ◽  
2012 ◽  
Vol 4 (4) ◽  
pp. 509-520 ◽  
Author(s):  
Leslie Alessandri ◽  
David Ouellette ◽  
Aima Acquah ◽  
Mathew Rieser ◽  
David LeBlond ◽  
...  
Keyword(s):  
Serum Clearance ◽  
Human Igg1

A human IgG1-K type M-protein with antibody activity against horse and rabbit α2-macroglobulin

1985 ◽  
Vol 149 (2-3) ◽  
pp. 205-214 ◽  
Author(s):  
Kiyotaka Fujita ◽  
Ikunosuke Sakurabayashi ◽  
Tadashi Kawai ◽  
Toshimi Sato
Keyword(s):  
M Protein ◽  
Antibody Activity ◽  
Α2 Macroglobulin ◽  
Human Igg1

Camelid single-domain antibodies raised by DNA immunization are potent inhibitors of EGFR signaling

2019 ◽  
Vol 476 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Martin A. Rossotti ◽  
Kevin A. Henry ◽  
Henk van Faassen ◽  
Jamshid Tanha ◽  
Deborah Callaghan ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Growth Factor Receptor ◽  
Single Domain ◽  
Dna Immunization ◽  
Egfr Signaling ◽  
High Affinity ◽  
Single Domain Antibodies ◽  
Human Igg1 ◽  
Protein Immunization

Abstract Up-regulation of epidermal growth factor receptor (EGFR) is a hallmark of many solid tumors, and inhibition of EGFR signaling by small molecules and antibodies has clear clinical benefit. Here, we report the isolation and functional characterization of novel camelid single-domain antibodies (sdAbs or VHHs) directed against human EGFR. The source of these VHHs was a llama immunized with cDNA encoding human EGFR ectodomain alone (no protein or cell boost), which is notable in that genetic immunization of large, outbred animals is generally poorly effective. The VHHs targeted multiple sites on the receptor's surface with high affinity (KD range: 1–40 nM), including one epitope overlapping that of cetuximab, several epitopes conserved in the cynomolgus EGFR orthologue, and at least one epitope conserved in the mouse EGFR orthologue. Interestingly, despite their generation against human EGFR expressed from cDNA by llama cells in vivo (presumably in native conformation), the VHHs exhibited wide and epitope-dependent variation in their apparent affinities for native EGFR displayed on tumor cell lines. As fusions to human IgG1 Fc, one of the VHH-Fcs inhibited EGFR signaling induced by EGF binding with a potency similar to that of cetuximab (IC50: ∼30 nM). Thus, DNA immunization elicited high-affinity, functional sdAbs that were vastly superior to those previously isolated by our group through protein immunization.

scholarly journals Combined Roles of Human IgG Subclass, Alternative Complement Pathway Activation, and Epitope Density in the Bactericidal Activity of Antibodies to Meningococcal Factor H Binding Protein

2011 ◽  
Vol 80 (1) ◽  
pp. 187-194 ◽  
Author(s):  
Serena Giuntini ◽  
Donald C. Reason ◽  
Dan M. Granoff
Keyword(s):  
Bactericidal Activity ◽  
Type Strain ◽  
Wild Type Strain ◽  
Factor H ◽  
Complement Pathway ◽  
Wild Type ◽  
Alternative Complement ◽  
Igg1 Mabs ◽  
Human Igg1 ◽  
Epitope Density

ABSTRACTMeningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.

Fucose Depletion from Human IgG1 Oligosaccharide Enhances Binding Enthalpy and Association Rate Between IgG1 and FcγRIIIa

2004 ◽  
Vol 336 (5) ◽  
pp. 1239-1249 ◽  
Author(s):  
Akira Okazaki ◽  
Emi Shoji-Hosaka ◽  
Kazuyasu Nakamura ◽  
Masako Wakitani ◽  
Kazuhisa Uchida ◽  
...  
Keyword(s):  
Association Rate ◽  
Human Igg1 ◽  
Binding Enthalpy

Thermodynamic and kinetic effects of human IgG1 defucosylation on IgG1-FcγRIIIa interaction

2006 ◽  
pp. 47-53
Author(s):  
Akira Okazaki ◽  
Emi Shoji ◽  
Kazuyasu Nakamura ◽  
Masako Wakitani ◽  
Kazuhisa Uchida ◽  
...  
Keyword(s):  
Human Igg1 ◽  
Kinetic Effects

Anti-virulence Bispecific Monoclonal Antibody Mediated Protection Against Pseudomonas aeruginosa Ventilator-Associated Pneumonia in a Rabbit Model

2021 ◽  
Author(s):  
Fábio Aguiar-Alves ◽  
Hoan N. Le ◽  
Vuvi G. Tran ◽  
Emmanuelle Gras ◽  
Trang Vu ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Rabbit Model ◽  
Arterial Oxygen ◽  
Rank Test ◽  
Ventilator Associated Pneumonia ◽  
Exact Test ◽  
Cytokines And Chemokines ◽  
Potential Clinical Utility ◽  
Human Igg1 ◽  
Type 3

Ventilator-associated pneumonia is an important clinical manifestation of the nosocomial pathogen Pseudomonas aeruginosa . We characterized the correlates of protection of MEDI3902, a bispecific human IgG1 mAb that targets the P. aeruginosa type-3-secretion PcrV protein and the Psl exopolysaccharide, in a rabbit model of ventilator-associated pneumonia using lung-protective, low-tidal volume mechanical ventilation. Rabbits infused with MEDI3902 prophylactically were protected, whereas those pretreated with irrelevant isotype-control IgG (c-IgG) succumbed between 12 and 44 hours post infection [100% (8/8) vs. 0% (8/8) survival, P <0.01 by log-rank test]. Lungs from rabbits pretreated with c-IgG, but not those with MEDI3902, had bilateral, multifocal areas of marked necrosis, hemorrhage, neutrophilic inflammatory infiltrate, diffuse fibrinous edema in alveolar spaces. All rabbits pretreated with c-IgG developed worsening bacteremia that peaked at the time of death, whereas only 38% (3/8) rabbits pretreated with MEDI3902 developed such high-grade bacteremia (two-sided Fisher’s exact test, P =0.026). Biomarkers associated with acute respiratory distress syndrome were evaluated longitudinally in blood samples collected every 2-4 hours to assess systemic pathophysiological changes in rabbits pretreated with MEDI3902 or c-IgG. Biomarkers were sharply increased or decreased in rabbits pretreated with c-IgG, but not those pretreated with MEDI3902, including ratio of arterial oxygen partial pressure to fractional inspired oxygen PaO 2 /FiO 2 <300, hypercapnia or hypocapnia, severe lactic acidosis, leukopenia and neutropenia. Cytokines and chemokines associated with ARDS were significantly downregulated in lungs from rabbits pretreated with MEDI3902 compared with c-IgG. These results suggest that MEDI3902 prophylaxis could have potential clinical utility for decreasing severity of P. aeruginosa ventilator-associated pneumonia.

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