Journal ArticleDOI
Glycosylation as a strategy to improve antibody-based therapeutics
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 clinicread more
Citations
More filters
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
Andrew C. Chan,Paul Carter +1 more
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
Abhinav A. Shukla,Jörg Thömmes +1 more
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
More filters
Journal ArticleDOI
Continuous cultures of fused cells secreting antibody of predefined specificity
G Köhler,C. Milstein +1 more
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.
Journal ArticleDOI
Humanization of an anti-p185HER2 antibody for human cancer therapy.
Paul Carter,L. G. Presta,Cornelia M. Gorman,John B. Ridgway,Dennis J. Henner,Wai Lee Wong,A. M. Rowland,Claire Kotts,M. E. Carver,H M Shepard +9 more
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.
Journal ArticleDOI
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
Robert L. Shields,Jadine Lai,Rodney G. Keck,Lori Y. O'Connell,Kyu Hong,Y. Gloria Meng,Stefanie Weikert,Leonard G. Presta +7 more
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.