Transgenic goats producing an improved version of cetuximab in milk

FASEB BioAdvances
Götz LaibleH. M. Meade

Abstract

Therapeutic monoclonal antibodies (mAbs) represent one of the most important classes of pharmaceutical proteins to treat human diseases. Most are produced in cultured mammalian cells which is expensive, limiting their availability. Goats, striking a good balance between a relatively short generation time and copious milk yield, present an alternative platform for the cost-effective, flexible, large-scale production of therapeutic mAbs. Here, we focused on cetuximab, a mAb against epidermal growth factor receptor, that is commercially produced under the brand name Erbitux and approved for anti-cancer treatments. We generated several transgenic goat lines that produce cetuximab in their milk. Two lines were selected for detailed characterization. Both showed stable genotypes and cetuximab production levels of up to 10 g/L. The mAb could be readily purified and showed improved characteristics compared to Erbitux. The goat-produced cetuximab (gCetuximab) lacked a highly immunogenic epitope that is part of Erbitux. Moreover, it showed enhanced binding to CD16 and increased antibody-dependent cell-dependent cytotoxicity compared to Erbitux. This indicates that these goats produce an improved cetuximab version with the potential for e...Continue Reading

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Citations

May 14, 2021·Stem Cell Research & Therapy·Birbal SinghMohammad Ali Moni

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Methods Mentioned

BETA
glycosylation
transgenic
FCS
PCR
X‐ray
column chromatography
electrophoresis
flow cytometry
ELISA
genotyping

Software Mentioned

AgResearch
BWA
REF
Bio
Integrative Genomic Viewer
Rad Quantity One
trimmomatic
Geneart
QuantaSoft Analysis Pro
Erbitux

Related Concepts

Related Feeds

Antibody-Dependent Cell Cytotoxicity

Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here.

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