which cells are responsible for antibody production

WHICH CELLS ARE RESPONSIBLE FOR ANTIBODY PRODUCTION FREE

Hence, the DHFR- mutant could not synthesize several molecules including glycine, thymine, and purine. The random mutagenesis which caused the alteration of the two alleles of the dihydrofolate reductase gene ( dhfr). The first system was established with the CHO-DXB11 variant, obtained by chemical mutagenesis with ethyl methanesulfonate of a CHO cell line. There are currently two main systems for the selection of transfected CHO clones. Typical selection markers in CHO – the DHFR system

While K1 was cloned directly from the original cell line and later found to lack a gene necessary for glycine synthesis, a deficiency that paved the way for the creation of mutants with high value for recombinant transfection and selection. For instance, CHO-S was obtained during the efforts of adapting CHO to the growth in suspension cultures, essential for the large-scale production of biopharmaceuticals.

Today, the most important CHO-derived cell lines include CHO-K1, CHO-S, CHO-DXB11, and CHO-DG44.ĬHO’s main variants were mostly obtained by random mutagenesis and selection of the original parental cell line. Interestingly, the ease of genetic manipulation by mutagenesis has led to the establishment of many CHO-derived daughter cell lines with improved properties. These cultures containing cells isolated from an ovary of a female Chinese hamster soon revealed to be resilient, fast-growing and quick to adapt to in vitro cultivation conditions. Chinese hamsters were first used as laboratory specimens as early as 1919, however, cell cultures were only obtained in the late 1950s by Theodore Puck (University of Colorado, USA). Interestingly, transfected mammalian cell lines are also prone to secreting the proteins to the medium, allowing researchers to obtain high production yields with reduced purification costs.Ĭhinese hamster ovary (CHO) cells Origin, antibody production, and cell derivatesĬHO cells are today industry’s most important workhorse for therapeutic protein production. This marked preference towards mammalian cells stirs from the fact that they have a proven track record for producing glycoproteins with established therapeutic efficiency. Cells used for these purposes are mostly from mammalian origin. Presently, recombinant technologies and genetic engineering have shaped the landscape of antibody production.

Ideally, these systems should also adapt to growth in suspension, as these conditions can be easily scalable for usage in large stirred-tank bioreactors, unlike the lab-scale practices of cultivating cells in adhesion cultures.

WHICH CELLS ARE RESPONSIBLE FOR ANTIBODY PRODUCTION FREE

free from contamination with pathogenic agents). Moreover, they should also guarantee product safety for human and animal use (i.e. For instance, they needed to be able to perform correct protein folding and adequate post-translational modifications. These allowed researchers to clone antibody-encoding genes into different expression hosts and to engineer these hosts for large-scale and long-term production.įrom an industrial point-of-view, these expression hosts needed to possess certain characteristics. However, these constraints started dissolving with the advent of recombinant technologies. These limitations have made early antibody production expensive and hindered its translation to large-scale therapeutic production. However, these hybrid cell lines were characterized by fluctuating production yields and frequently lost the antibody-encoding genes during long-term cultivation. Early approaches to antibody production – cells and methodologiesĮarly approaches to the production of monoclonal antibodies relied on hybridoma cell lines.

Which cells are responsible for antibody production