Monoclonal Antibody Aggregation Intermediates Visualized by Atomic Force Microscopy

Lee, Hanjoo; Kirchmeier, Marc; Mach, H.

doi:10.1002/jps.22279

Cited by 26 publications

(12 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the range of possible aggregation pathways has not been elucidated experimentally for many proteins, it has been mapped out to a reasonable extent for at least one MAb [25], and a globular protein under analogous solution conditions [31]. Based on these examples, as one increases the pH far above the pI of a protein, and/or reduces the ionic strength of the solution, protein aggregates do not grow as easily, and vice-versa (Figure 2), consistent with results from a number of MAb systems [25,32,39–44], an eye lens crystallin [36,45], an aggregation-prone cytokine [46,22], and model globular proteins [34,31]. …”

Section: Which Mechanisms Prevail?supporting

confidence: 80%

“…Schematic illustrating shifts in aggregation mechanisms and examples of aggregates that do not grow easily (see also Box 2), to those grown by monomer addition (lower left image, from [46]), aggregate agglomeration to form globular aggregates (middle image, from [44]), and aggregate phase separation to form macroscopic particles (upper image, from [87]].…”

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

Therapeutic protein aggregation: mechanisms, design, and control

Roberts

2014

Trends in Biotechnology

356

309

View full text Add to dashboard Cite

While it is well known that proteins are only marginally stable in their folded states, it is often less well appreciated that most proteins are inherently aggregation-prone in their unfolded or partially unfolded states, and the resulting aggregates can be extremely stable and long-lived. For therapeutic proteins, aggregates are a significant risk factor for deleterious immune responses in patients, and can form via a variety of mechanisms. Controlling aggregation using a mechanistic approach may allow improved design of therapeutic protein stability, as a complement to existing design strategies that target desired protein structures and function. Recent results highlight the importance of balancing protein environment with the inherent aggregation propensities of polypeptide chains.

show abstract

Section: Which Mechanisms Prevail?supporting

confidence: 80%

Section: Figurementioning

confidence: 99%

Therapeutic protein aggregation: mechanisms, design, and control

Roberts

2014

Trends in Biotechnology

356

309

View full text Add to dashboard Cite

show abstract

“…SEM combined with energy dispersive X-ray analysis can provide certain information on the chemical composition of a particle, e.g., the elements present within the particle [70,71]. Atomic force microscopy (AFM) enables additional characterization of particle morphology and topography in the size range of about 0.1 nme100 mm by applying a 3D topographical scanning [72,73].…”

Section: Microscopic Techniquesmentioning

confidence: 99%

Subvisible and Visible Particle Analysis in Biopharmaceutical Research and Development

Hawe¹,

Zölls²,

Freitag³

et al. 2015

Biophysical Characterization of Proteins in Developing Biopharmaceuticals

View full text Add to dashboard Cite

“…In a recent future the use of sophisticated techniques, such as atomic force microscopy (utilized to unfold proteins mechanically [43,44]) or single-molecule fluorescence (able to detect the behaviour of single macromolecules, otherwise masked when the whole molecule population is considered) [45,46] may provide, together with computational approaches, a remarkable contribution for better defining the energy landscapes and probing the 'new view' concept in protein folding. However, further studies are necessary for defining some still unclear aspects of the process.…”

Section: Protein Folding: 'Classical View' Vs 'New View'mentioning

confidence: 99%