Aggregates, Crystals, Gels, and Amyloids: Intracellular and Extracellular Phenotypes at the Crossroads of Immunoglobulin Physicochemical Property and Cell Physiology
Open Access
- 5 March 2013
- journal article
- review article
- Published by Hindawi Limited in International Journal of Cell Biology
- Vol. 2013, 1-22
- https://doi.org/10.1155/2013/604867
Abstract
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.Keywords
This publication has 167 references indexed in Scilit:
- Variable Region Identical Immunoglobulins Differing in Isotype Express Different Paratopes*Journal of Biological Chemistry, 2012
- Pathological crystallization of human immunoglobulinsProceedings of the National Academy of Sciences of the United States of America, 2012
- Isotype modulates epitope specificity, affinity, and antiviral activities of anti–HIV-1 human broadly neutralizing 2F5 antibodyProceedings of the National Academy of Sciences of the United States of America, 2012
- Increasing Serum Half-life and Extending Cholesterol Lowering in Vivo by Engineering Antibody with pH-sensitive Binding to PCSK9*Online Journal of Public Health Informatics, 2012
- Crystal-Storing Histiocytosis: Report of a Case, Review of the Literature (80 Cases) and a Proposed ClassificationHead and Neck Pathology, 2012
- In Vivo Crystallization of Human IgG in the Endoplasmic Reticulum of Engineered Chinese Hamster Ovary (CHO) CellsOnline Journal of Public Health Informatics, 2011
- Two Structural and Functional Domains of MESD Required for Proper Folding and Trafficking of LRP5/6Structure, 2011
- An Unfolded CH1 Domain Controls the Assembly and Secretion of IgG AntibodiesMolecular Cell, 2009
- Conditional deletion of the MHC class I-related receptor FcRn reveals the sites of IgG homeostasis in miceProceedings of the National Academy of Sciences of the United States of America, 2009
- Engineered antibody fragments and the rise of single domainsNature Biotechnology, 2005