Detection and characterization of subvisible aggregates of monoclonal lgG in serum
(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:
http://hdl.handle.net/1854/LU-2125255
- author
- Vasco Filipe, Robert Poole, Olubukayo Oyetayo, Kevin Braeckmans UGent and Wim Jiskoot
- organization
- year
- 2012
- 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
- 2017-04-13 14:44:14
@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.