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Journal ArticleDOI

Glycosylation as a strategy to improve antibody-based therapeutics

Roy Jefferis
- 01 Mar 2009 - 
- Vol. 8, Iss: 3, pp 226-234
TLDR
Current knowledge of methods and avenues for their exploitation in the clinic are summarized, which allow the production of rMAbs bearing pre-selected oligosaccharides — glycoforms — to provide maximum efficacy for a given disease indication.
Abstract
To date, more than 20 recombinant immunoglobulin G (IgG) antibody therapeutics are licensed for the treatment of various diseases The mechanism of action of recombinant monoclonal antibodies (rMAbs) has been extensively investigated and several distinct pathways have been defined; selective activation of specific pathways may optimize clinical outcomes for different diseases, such as cancer and chronic inflammation Human IgG is a glycoprotein with oligosaccharides attached at a single site These are essential to the mode of action of rMAbs, and the antibody efficacy can vary depending on the particular oligosaccharide that is attached Methods are now becoming available that allow the production of rMAbs bearing pre-selected oligosaccharides - glycoforms - to provide maximum efficacy for a given disease indication This Review summarizes current knowledge of these methods and avenues for their exploitation in the clinic

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Citations
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Journal ArticleDOI

Biological Roles of Glycans

TL;DR: It is time for the diverse functional roles of glycans to be fully incorporated into the mainstream of biological sciences, as they are no different from other major macromolecular building blocks of life, simply more rapidly evolving and complex.
Journal ArticleDOI

Glycosylation in health and disease.

TL;DR: The broad role of glycans in immunity, cancer, xenotransplantation and glomerular filtration and the potential of ‘glycomedicine’ are discussed.
Journal ArticleDOI

Therapeutic antibodies for autoimmunity and inflammation

TL;DR: How key insights obtained from the development of therapeutic antibodies complemented by newer antibody engineering technologies are delivering a second generation of therapeutic antibody with promise for greater clinical efficacy and safety is reviewed.
Journal ArticleDOI

Strategies and challenges for the next generation of therapeutic antibodies

TL;DR: Strategies to select the best therapeutic antigen targets, to optimize the structure of IgG antibodies and to design related or new structures with additional functions are discussed.
Journal ArticleDOI

Recent Advances in Large-Scale Production of Monoclonal Antibodies and Related Proteins

TL;DR: The current state-of-the-art industrial production processes, focusing on downstream technologies, for antibodies and antibody-related products are reviewed and future avenues for evolution are discussed.
References
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Journal ArticleDOI

Continuous cultures of fused cells secreting antibody of predefined specificity

TL;DR: The derivation of a number of tissue culture cell lines which secrete anti-sheep red blood cell (SRBC) antibodies is described here, made by fusion of a mouse myeloma and mouse spleen cells from an immunised donor.
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Humanization of an anti-p185HER2 antibody for human cancer therapy.

TL;DR: The murine monoclonal antibody mumAb4D5, directed against human epidermal growth factor receptor 2 (p 185HER2), specifically inhibits proliferation of human tumor cells overexpressing p185HER2, but the efficacy of mumAb 4D5 in human cancer therapy is likely to be limited by a human anti-mouse antibody response and lack of effector functions.
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Fcγ receptors as regulators of immune responses

TL;DR: Recent studies addressing the multifaceted roles of FcRs for IgG (FcγRs) in the immune system are discussed and how this knowledge could be translated into novel therapeutic strategies to treat human autoimmune, infectious or malignant diseases are discussed.
Journal ArticleDOI

Lack of Fucose on Human IgG1 N-Linked Oligosaccharide Improves Binding to Human FcγRIII and Antibody-dependent Cellular Toxicity

TL;DR: Antibody-dependent cellular cytot toxicity assays using purified peripheral blood monocytes or natural killer cells from several donors showed enhanced cytotoxicity, especially evident at lower antibody concentrations.
Journal ArticleDOI

FcRn: the neonatal Fc receptor comes of age

TL;DR: The neonatal Fc receptor for IgG (FcRn) has been well characterized in the transfer of passive humoral immunity from a mother to her fetus and throughout life, FcRm protects IgG from degradation, thereby explaining the long half-life of this class of antibody in the serum.
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