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Detection and characterization of subvisible aggregates of monoclonal lgG in serum

Vasco Filipe, Robert Poole, Olubukayo Oyetayo, Kevin Braeckmans UGent and Wim Jiskoot (2012) PHARMACEUTICAL RESEARCH. 29(8). p.2202-2212
abstract
To detect and characterize the aggregation of therapeutic monoclonal antibodies in undiluted biological fluids. Fluorescently labeled subvisible IgG aggregates formed by applying either heat stress or by pH-shift were investigated immediately after addition to human serum, and after 24 h. Unstressed and stressed IgG formulations were analyzed by fluorescence single particle tracking, confocal laser scanning microscopy and flow cytometry. Unstressed formulations remained free from subvisible aggregates in serum, whereas heat-stressed and pH-shift stressed formulations showed dissimilar aggregation behaviors. The aggregation profile of the heat-stressed formulation diluted in serum remained practically the same as the one diluted in buffer, even after the 24 h incubation period. The pH-shift stressed formulation had strikingly smaller and more numerous subvisible aggregates immediately after dilution in serum compared to buffer. These aggregates became noticeably larger in both diluents after 24 h, but in serum they appeared to be formed by other types of constituents than the labeled protein itself. These results show that subvisible therapeutic protein aggregates may undergo changes in number, type and size distribution upon contact with human serum. This emphasizes the importance of analytical strategies for monitoring aggregation in undiluted biological fluids.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
confocal laser scanning microscopy, flow cytometry, monoclonal antibody, serum, subvisible protein aggregates, fluorescence single particle tracking, PROTEIN AGGREGATION, ANTIBODY, IMMUNOGENICITY, PARTICLES, NANOPARTICLES, PERSPECTIVE, TRACKING, ALBUMIN
journal title
PHARMACEUTICAL RESEARCH
Pharm. Res.
volume
29
issue
8
pages
2202 - 2212
Web of Science type
Article
Web of Science id
000306547300015
JCR category
PHARMACOLOGY & PHARMACY
JCR impact factor
4.742 (2012)
JCR rank
25/259 (2012)
JCR quartile
1 (2012)
ISSN
0724-8741
DOI
10.1007/s11095-012-0749-x
project
Center for nano- and biophotonics (NB-Photonics)
language
English
UGent publication?
yes
classification
A1
copyright statement
I have retained and own the full copyright for this publication
id
2125255
handle
http://hdl.handle.net/1854/LU-2125255
date created
2012-05-31 14:58:27
date last changed
2014-05-26 09:49:27
@article{2125255,
  abstract     = {To detect and characterize the aggregation of therapeutic monoclonal antibodies in undiluted biological fluids. 
Fluorescently labeled subvisible IgG aggregates formed by applying either heat stress or by pH-shift were investigated immediately after addition to human serum, and after 24 h. Unstressed and stressed IgG formulations were analyzed by fluorescence single particle tracking, confocal laser scanning microscopy and flow cytometry. 
Unstressed formulations remained free from subvisible aggregates in serum, whereas heat-stressed and pH-shift stressed formulations showed dissimilar aggregation behaviors. The aggregation profile of the heat-stressed formulation diluted in serum remained practically the same as the one diluted in buffer, even after the 24 h incubation period. The pH-shift stressed formulation had strikingly smaller and more numerous subvisible aggregates immediately after dilution in serum compared to buffer. These aggregates became noticeably larger in both diluents after 24 h, but in serum they appeared to be formed by other types of constituents than the labeled protein itself. 
These results show that subvisible therapeutic protein aggregates may undergo changes in number, type and size distribution upon contact with human serum. This emphasizes the importance of analytical strategies for monitoring aggregation in undiluted biological fluids.},
  author       = {Filipe, Vasco and Poole, Robert and Oyetayo, Olubukayo and Braeckmans, Kevin and Jiskoot, Wim},
  issn         = {0724-8741},
  journal      = {PHARMACEUTICAL RESEARCH},
  keyword      = {confocal laser scanning microscopy,flow cytometry,monoclonal antibody,serum,subvisible protein aggregates,fluorescence single particle tracking,PROTEIN AGGREGATION,ANTIBODY,IMMUNOGENICITY,PARTICLES,NANOPARTICLES,PERSPECTIVE,TRACKING,ALBUMIN},
  language     = {eng},
  number       = {8},
  pages        = {2202--2212},
  title        = {Detection and characterization of subvisible aggregates of monoclonal lgG in serum},
  url          = {http://dx.doi.org/10.1007/s11095-012-0749-x},
  volume       = {29},
  year         = {2012},
}

Chicago
Filipe, Vasco, Robert Poole, Olubukayo Oyetayo, Kevin Braeckmans, and Wim Jiskoot. 2012. “Detection and Characterization of Subvisible Aggregates of Monoclonal lgG in Serum.” Pharmaceutical Research 29 (8): 2202–2212.
APA
Filipe, V., Poole, R., Oyetayo, O., Braeckmans, K., & Jiskoot, W. (2012). Detection and characterization of subvisible aggregates of monoclonal lgG in serum. PHARMACEUTICAL RESEARCH, 29(8), 2202–2212.
Vancouver
1.
Filipe V, Poole R, Oyetayo O, Braeckmans K, Jiskoot W. Detection and characterization of subvisible aggregates of monoclonal lgG in serum. PHARMACEUTICAL RESEARCH. 2012;29(8):2202–12.
MLA
Filipe, Vasco, Robert Poole, Olubukayo Oyetayo, et al. “Detection and Characterization of Subvisible Aggregates of Monoclonal lgG in Serum.” PHARMACEUTICAL RESEARCH 29.8 (2012): 2202–2212. Print.