Aggregates, crystals, gels, and amyloids: intracellular and extracellular phenotypes at the crossroads of immunoglobulin physicochemical property and cell physiology.

Authors:
Haruki Hasegawa, PhD
Haruki Hasegawa, PhD
Amgen Inc.
Principal Scientist
Protein trafficking Protein biosynthesis
South San Francisco, CA | United States

Int J Cell Biol 2013 5;2013:604867. Epub 2013 Mar 5.

Department of Therapeutic Discovery, Amgen Inc., 1201 Amgen Court West, Seattle, WA 98119, USA.

Recombinant immunoglobulins comprise an important class of human therapeutics. Although specific immunoglobulins can be purposefully raised against desired antigen targets by various methods, identifying an immunoglobulin clone that simultaneously possesses potent therapeutic activities and desirable manufacturing-related attributes often turns out to be challenging. The variable domains of individual immunoglobulins primarily define the unique antigen specificities and binding affinities inherent to each clone. The primary sequence of the variable domains also specifies the unique physicochemical properties that modulate various aspects of individual immunoglobulin life cycle, starting from the biosynthetic steps in the endoplasmic reticulum, secretory pathway trafficking, secretion, and the fate in the extracellular space and in the endosome-lysosome system. Because of the diverse repertoire of immunoglobulin physicochemical properties, some immunoglobulin clones' intrinsic properties may manifest as intriguing cellular phenotypes, unusual solution behaviors, and serious pathologic outcomes that are of scientific and clinical importance. To gain renewed insights into identifying manufacturable therapeutic antibodies, this paper catalogs important intracellular and extracellular phenotypes induced by various subsets of immunoglobulin clones occupying different niches of diverse physicochemical repertoire space. Both intrinsic and extrinsic factors that make certain immunoglobulin clones desirable or undesirable for large-scale manufacturing and therapeutic use are summarized.

Download full-text PDF

Source
http://dx.doi.org/10.1155/2013/604867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603282PMC

Still can't find the full text of the article?

We can help you send a request to the authors directly.
March 2013
3 Reads
6 Citations

Publication Analysis

Top Keywords

intracellular extracellular
8
extracellular phenotypes
8
immunoglobulin physicochemical
8
physicochemical properties
8
immunoglobulin clones
8
variable domains
8
immunoglobulin
7
endoplasmic reticulum
4
steps endoplasmic
4
reticulum secretory
4
secretion fate
4
fate extracellular
4
trafficking secretion
4
secretory pathway
4
pathway trafficking
4
space endosome-lysosome
4
properties immunoglobulin
4
immunoglobulin clones'
4
clones' intrinsic
4
intrinsic properties
4

References

(Supplied by CrossRef)
Article in Immunological Reviews
Immunological Reviews 1988
Article in British Medical Journal
British Medical Journal 1890
Article in The Lancet
The Lancet 1899
Article in The Journal of Experimental Medicine
The Journal of Experimental Medicine 1923
Article in Archives of Pathology
Archives of Pathology 1931
Article in The Journal of Medical Research
The Journal of Medical Research 1921
Article in Journal of Clinical Pathology
Journal of Clinical Pathology 1949
Article in Anatomical Record
Anatomical Record 1942
Article in Journal of Clinical Pathology
Journal of Clinical Pathology 1970
Article in Investigative Ophthalmology
Investigative Ophthalmology 1969

Similar Publications