Recombinant Proteins and Monoclonal Antibodies

Overview

Journal Adv Biochem Eng Biotechnol

Specialties Biochemistry
Biotechnology

Date 2017 Oct 27

PMID 29071407

Citations 6

Authors

Roy Jefferis

Affiliations

Soon will be listed here.

Abstract

The human genome has become a subject of public interest, whilst the proteome remains the province of specialists. Less appreciated is the human glycoprotein (GP) repertoire (proteoglycome!); however, some 50% of open reading frame genes encode for proteins (P) that may accept the addition of N-linked and/or O-linked sugar chains (oligosaccharides). It is established that the attachment of defined oligosaccharide structures impacts mechanisms of action (MoAs), pharmacokinetics, pharmacodynamics, etc., and is a critical quality attribute (CQA) for recombinant GP therapeutics. The oligosaccharide structure attached at a given site may exhibit structural heterogeneity, and individual structures (glycoforms) may modulate MoAs. The biopharmaceutical industry is challenged, therefore, to produce recombinant GP therapeutics that have structural fidelity to the natural (endogenous) molecule, in non-human cells. Multiple production platforms have been developed that, in addition to the natural glycoform, may produce unnatural glycoforms, including sugar residues that can be immunogenic in human subjects. Following a general introduction to the field, this review discusses glycosylation of recombinant monoclonal antibodies (mAbs), the contribution of glycoforms to MoAs and the development of customised mAb therapeutic glycoforms to optimise MoAs for individual disease indications.

Citing Articles

Multilayer Nanocarrier for the Codelivery of Interferons: A Promising Strategy for Biocompatible and Long-Acting Antiviral Treatment.

Ramos T, Villacis-Aguirre C, Sandoval F, Martin-Solano S, Manrique-Suarez V, Rodriguez H Pharmaceutics. 2024; 16(11).

PMID: 39598474 PMC: 11597830. DOI: 10.3390/pharmaceutics16111349.

Cell-free -glycosylation of peptides using synthetic lipid-linked hybrid and complex -glycans.

Wenzel L, Hoffmann M, Rapp E, Rexer T, Reichl U Front Mol Biosci. 2023; 10:1266431.

PMID: 37767159 PMC: 10520871. DOI: 10.3389/fmolb.2023.1266431.

Core fucosylation and its roles in gastrointestinal glycoimmunology.

Zhang N, Zhao L, Zhang Q, Fang H, Song W, Li W World J Gastrointest Oncol. 2023; 15(7):1119-1134.

PMID: 37546555 PMC: 10401475. DOI: 10.4251/wjgo.v15.i7.1119.

The Role of Clinical Glyco(proteo)mics in Precision Medicine.

van der Burgt Y, Wuhrer M Mol Cell Proteomics. 2023; 22(6):100565.

PMID: 37169080 PMC: 10326703. DOI: 10.1016/j.mcpro.2023.100565.

Glycobiology of rheumatic diseases.

Kissel T, Toes R, Huizinga T, Wuhrer M Nat Rev Rheumatol. 2022; 19(1):28-43.

PMID: 36418483 PMC: 9684870. DOI: 10.1038/s41584-022-00867-4.

References

Gupta S, Bhandari B, Shrestha A, Biswal B, Palaniappan C, Malhotra S . Mammalian zona pellucida glycoproteins: structure and function during fertilization. Cell Tissue Res. 2012; 349(3):665-78. DOI: 10.1007/s00441-011-1319-y. View

Drickamer K, Taylor M . Recent insights into structures and functions of C-type lectins in the immune system. Curr Opin Struct Biol. 2015; 34:26-34. PMC: 4681411. DOI: 10.1016/j.sbi.2015.06.003. View

Monticelli M, Ferro T, Jaeken J, Dos Reis Ferreira V, Videira P . Immunological aspects of congenital disorders of glycosylation (CDG): a review. J Inherit Metab Dis. 2016; 39(6):765-780. DOI: 10.1007/s10545-016-9954-9. View

Laine R . A calculation of all possible oligosaccharide isomers both branched and linear yields 1.05 x 10(12) structures for a reducing hexasaccharide: the Isomer Barrier to development of single-method saccharide sequencing or synthesis systems. Glycobiology. 1994; 4(6):759-67. DOI: 10.1093/glycob/4.6.759. View

Higel F, Seidl A, Sorgel F, Friess W . N-glycosylation heterogeneity and the influence on structure, function and pharmacokinetics of monoclonal antibodies and Fc fusion proteins. Eur J Pharm Biopharm. 2016; 100:94-100. DOI: 10.1016/j.ejpb.2016.01.005. View

Walsh D, Mathews M, Mohr I . Tinkering with translation: protein synthesis in virus-infected cells. Cold Spring Harb Perspect Biol. 2012; 5(1):a012351. PMC: 3579402. DOI: 10.1101/cshperspect.a012351. View

Stewart-Jones G, Soto C, Lemmin T, Chuang G, Druz A, Kong R . Trimeric HIV-1-Env Structures Define Glycan Shields from Clades A, B, and G. Cell. 2016; 165(4):813-26. PMC: 5543418. DOI: 10.1016/j.cell.2016.04.010. View

Piacente F, Gaglianone M, Laugieri M, Tonetti M . The Autonomous Glycosylation of Large DNA Viruses. Int J Mol Sci. 2015; 16(12):29315-28. PMC: 4691112. DOI: 10.3390/ijms161226169. View

Adolf G, Kalsner I, Ahorn H, Cantell K . Natural human interferon-alpha 2 is O-glycosylated. Biochem J. 1991; 276 ( Pt 2):511-8. PMC: 1151121. DOI: 10.1042/bj2760511. View

10.

Jonasch E, Haluska F . Interferon in oncological practice: review of interferon biology, clinical applications, and toxicities. Oncologist. 2001; 6(1):34-55. DOI: 10.1634/theoncologist.6-1-34. View

11.

Welte K . G-CSF: filgrastim, lenograstim and biosimilars. Expert Opin Biol Ther. 2014; 14(7):983-93. DOI: 10.1517/14712598.2014.905537. View

12.

Okamoto M, Nakai M, Nakayama C, Yanagi H, Matsui H, Noguchi H . Purification and characterization of three forms of differently glycosylated recombinant human granulocyte-macrophage colony-stimulating factor. Arch Biochem Biophys. 1991; 286(2):562-8. DOI: 10.1016/0003-9861(91)90080-3. View

13.

Zhang Q, Johnston E, Shieh J, Moore M, Danishefsky S . Synthesis of granulocyte-macrophage colony-stimulating factor as homogeneous glycoforms and early comparisons with yeast cell-derived material. Proc Natl Acad Sci U S A. 2014; 111(8):2885-90. PMC: 3939888. DOI: 10.1073/pnas.1400140111. View

14.

Bhatacharya P, Pandey G, Mukherjee K . Production and purification of recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) from high cell density cultures of Pichia pastoris. Bioprocess Biosyst Eng. 2007; 30(5):305-12. DOI: 10.1007/s00449-007-0124-1. View

15.

Seppala M, Koistinen H, Koistinen R, Chiu P, Yeung W . Glycosylation related actions of glycodelin: gamete, cumulus cell, immune cell and clinical associations. Hum Reprod Update. 2007; 13(3):275-87. DOI: 10.1093/humupd/dmm004. View

16.

Yeung W, Lee K, Koistinen R, Koistinen H, Seppala M, Chiu P . Effects of glycodelins on functional competence of spermatozoa. J Reprod Immunol. 2009; 83(1-2):26-30. DOI: 10.1016/j.jri.2009.04.012. View

17.

Lee C, Pang P, Yeung W, Tissot B, Panico M, Lao T . Effects of differential glycosylation of glycodelins on lymphocyte survival. J Biol Chem. 2009; 284(22):15084-96. PMC: 2685690. DOI: 10.1074/jbc.M807960200. View

18.

Seppala M, Koistinen H, Koistinen R, Hautala L, Chiu P, Yeung W . Glycodelin in reproductive endocrinology and hormone-related cancer. Eur J Endocrinol. 2008; 160(2):121-33. DOI: 10.1530/EJE-08-0756. View

19.

Jelkmann W . Erythropoietin: structure, control of production, and function. Physiol Rev. 1992; 72(2):449-89. DOI: 10.1152/physrev.1992.72.2.449. View

20.

Gong B, Burnina I, Stadheim T, Li H . Glycosylation characterization of recombinant human erythropoietin produced in glycoengineered Pichia pastoris by mass spectrometry. J Mass Spectrom. 2013; 48(12):1308-17. DOI: 10.1002/jms.3291. View