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The present state of the art in expression, production and characterization of monoclonal antibodies

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Abstract

Monoclonal antibodies (MAb’s) have become one the most powerful therapeutic and diagnostic tools in modern medicine. Some estimates target the worldwide market of MAb’s on the order of $125 billion in the next four years. Recent advances in molecular biology, immunology, and development of robust production platforms will drive the development of more MAb’s suitable to treat an ever increasing number of disease states. This circumstance combined with the fact that many of the original antibody therapies from the 1980s and 1990s will soon be coming off patent will attract a great deal of investment in the development of larger industrial facilities to increase monoclonal antibody to meet increasing demand. In this review, the present state of the science that underlies the development of new antibodies therapies in Chinese hamster ovary cells combined with a description of the present challenges facing the industry in terms of the limitations of output and compliance with current good manufacturing practices and FDA regulations. Also addressed are future challenges to overcome production bottlenecks, description of critical quality control attributes particular to antibodies, and detailed treatment of scale-up considerations.

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Abbreviations

pDO:

Percent dissolved oxygen

\(\hbox {pCO}_{2}\) :

Percent dissolved \(\hbox {CO}_{2}\)

HPLC:

High performance liquid chromatography

RP-HPLC:

Reverse phase-high performance liquid chromatography

CHO:

Chinese hamster ovary

MAb:

Monoclonal antibody

MTX:

Methotrexate

MeOH:

Methanol

ACN:

Acetonitrile

HGPRT:

Hypoxanthine-guanine-phosphoribosyl-transferase

HAT Medium:

Hypoxanthine-aminopterin-thymidine medium

MALDI:

Matrix-assisted laser desorption/ionization

MALDI-TOF:

Matrix-assisted laser desorption/ionization-time-of-flight

CEX:

Cation exchange chromatography

AEX:

Anion exchange chromatography

IEC:

Ion exchange chromatography

HIC:

Hydrophobic interaction chromatography

ELISA:

Enzyme linked immunosorbent assay

FT-ICR:

Fourier ion cyclotron resonance

DHFR:

Dihydrofolate reductase

GS:

Glutamine synthase

IgG:

Immunoglobulin G

TFF:

Tangential flow filtration, spin filter

ATF:

Alternating tangential flow

ESI:

Electrospray ionization

FT-ICR:

Fourier transform ion cyclotron resonance

LTQ-Orbitrap:

Hybrid linear quadropole ion-trap-orbitrap

DFPS:

Depth filter perfusion system

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    Christopher L. Gaughan

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Gaughan, C.L. The present state of the art in expression, production and characterization of monoclonal antibodies. Mol Divers 20, 255–270 (2016). https://doi.org/10.1007/s11030-015-9625-z

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