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Functional role of carbohydrate residues in human immunoglobulin G and therapeutic monoclonal antibodies

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Abstract

Therapeutic monoclonal antibodies (TMA) provide an important means for treating diseases that were previously considered untreatable. Currently more than 40 full-size TMAs created primarily based on immunoglobulin G1 are widely used for treating various illnesses. Glycosylation of TMA is among other numerous factors that affect their biological activity, effector functions, immunogenicity, and half-life in the patient’s serum. The importance of carbohydrate residues for activity of human serum immunoglobulin and TMA produced in animal cells is considered in this review, with emphasis given to N-glycosylation of the Fc fragment of the antibody.

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Abbreviations

ADCC:

antibody-dependent cell cytotoxicity

ADCP:

antibody-dependent cellular phagocytosis

Asn297:

asparagine at position 297 of amino acid sequence of the IgG heavy chain

CDC:

complement-dependent cytotoxicity

CH:

constant domain of the heavy chain

CL:

constant domain of the light chain

CMP-Neu5Ac:

CMP-acetylneuraminic acid

EMA:

European Medicines Agency

ER:

endoplasmic reticulum

Fab-fragment:

fragment antigen binding

Fc:

fragment crystallizable

FDA:

United States Food and Drug Administration

Fuc:

fucose

FUT8:

a1,6-fucosyltransferase

α-Gal:

galactose-α1,3-galactose

GalT:

β-N-acetylglycopeptide β-1,4-galactosyltransferase

GalNAc:

N-acetylgalactosamine

GCS I and II:

mannosyl-oligosaccharide glycosidase I and II

Glc:

glucose

GlcNAc:

N-acetylglucosamine

GM II:

Golgi a-mannosidase II

GNT I:

α-1,3-mannosyl-glucoprotein 2-β-N-acetylglucosaminyltransferase

GNT II:

α-1,6-mannosyl-glucoprotein 2-β-N-acetylglucosaminyltransferase

HER2:

human epidermal growth factor receptor 2

HR:

hinge region

HVR:

hypervariable region

Ig:

immunoglobulin

IgG:

immunoglobulin class G

Man:

mannose

MNS:

mannosidase

Neu5Gc:

glycolylneuraminic acid

NK:

natural killer cells

OST:

oligosaccharyltransferase

SIAT:

β-galactoside α-2,3/6-sialyltransferase

TMA:

therapeutic monoclonal antibodies

TNFα:

tumor necrosis factor a

VH :

variable domain of the heavy chain

VL :

variable domain of the light chain

ZFN:

zinc finger nuclease

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Authors and Affiliations

  1. Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991, Moscow, Russia

    Y. L. Dorokhov, E. V. Sheshukova, E. N. Kosobokova, A. V. Shindyapina, V. S. Kosorukov & T. V. Komarova

  2. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991, Moscow, Russia

    Y. L. Dorokhov, A. V. Shindyapina & T. V. Komarova

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  1. Y. L. Dorokhov
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  2. E. V. Sheshukova
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Original Russian Text © Y. L. Dorokhov, E. V. Sheshukova, E. N. Kosobokova, A. V. Shindyapina, V. S. Kosorukov, T. V. Komarova, 2016, published in Biokhimiya, 2016, Vol. 81, No. 8, pp. 1069-1090.

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Dorokhov, Y.L., Sheshukova, E.V., Kosobokova, E.N. et al. Functional role of carbohydrate residues in human immunoglobulin G and therapeutic monoclonal antibodies. Biochemistry Moscow 81, 835–857 (2016). https://doi.org/10.1134/S0006297916080058

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