title: Modulating carbohydrate-protein interactions through glycoengineering of monoclonal antibodies to impact cancer physiology.
abstract: Diverse glycans on proteins impact cell and organism physiology, along with drug activity. Since many protein-based biotherapeutics are glycosylated and these glycans have biological activity, there is a desire to engineer glycosylation for recombinant protein-based biotherapeutics. Engineered glycosylation can impact the recombinant protein efficacy and also influence many cell pathways by first changing glycan-protein interactions and consequently modulating disease physiologies. However, its complexity is enormous. Recent advances in glycoengineering now make it easier to modulate protein-glycan interactions. Here, we discuss how engineered glycans contribute to therapeutic monoclonal antibodies (mAbs) in the treatment of cancers, how these glycoengineered therapeutic mAbs affect the transformed phenotypes and downstream cell pathways. Furthermore, we suggest how systems biology can help in the next generation mAb glycoengineering process by aiding in data analysis and guiding engineering efforts to tailor mAb glycan and ultimately drug efficacy, safety and affordability.
authors.affiliation: Department of Pediatrics, University of California, San Diego, CA, USA; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, CA, USA.
authors.forename: Austin Wt
authors.initials: AW
authors.lastname: Chiang
authors.affiliation: Department of Pediatrics, University of California, San Diego, CA, USA; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, CA, USA; Department of Bioengineering, University of California, San Diego, CA, USA.
authors.forename: Shangzhong
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pediatrics, University of California, San Diego, CA, USA; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, CA, USA.
authors.forename: Philipp N
authors.initials: PN
authors.lastname: Spahn
authors.affiliation: Department of Pediatrics, University of California, San Diego, CA, USA; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, CA, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Richelle
authors.affiliation: Department of Pediatrics, University of California, San Diego, CA, USA; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, CA, USA; Department of Bioengineering, University of California, San Diego, CA, USA.
authors.forename: Chih-Chung
authors.initials: CC
authors.lastname: Kuo
authors.affiliation: Department of Pediatrics, University of California, San Diego, CA, USA; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, CA, USA.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Samoudi
authors.affiliation: Department of Pediatrics, University of California, San Diego, CA, USA; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, CA, USA. Electronic address: nlewisres@ucsd.edu.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Lewis
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D011134:Polysaccharides / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D011134:Polysaccharides