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Brief Report

High level expression of functional human IgMs in human PER.C6® cells

Anna Tchoudakova, Frank Hensel, Alec Murillo, Bernie Eng, Marketa Foley, Lakee Smith, Frank Schoenen, Antonia Hildebrand, Arndt-René Kelter, Leodevico L. Ilag, H. Peter Vollmers, Stephanie Brandlein, Jane McIninch, John Chon, Gene Lee and Marco Cacciuttolo

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Natural IgM antibodies play an important role in the body’s defense mechanisms against transformed cells in the human body and are currently being exploited both in prognoses of malignant lesions and in the therapy of cancer patients. However, despite growing interest and clinical promise, thus far the IgM class of antibodies has failed to gain widespread commercial interest as these are considered to be difficult to produce recombinantly.  IgMs are polymeric and have a relatively large mass. In addition, IgM molecules are heavily glycosylated and, when produced in non-human cell lines, they may contain non-human glycan structures which may be potentially immunogenic. Clearly, production systems capable of expressing human recombinant IgM antibodies are needed.  We have successfully used PER.C6® cells – a human cell line - to generate three separate human recombinant monoclonal IgMs in suspension cultures in protein-free medium. All three of the IgMs were constructed with joining (J) chain and were expressed in the pentameric form. One of the IgMs was also expressed as a hexamer without J chain. Clones with cell specific productivities greater than 20 pg/cell/day were generated, which led to yields of 0.5 g/L to 2g/L in fed-batch production. All the IgMs expressed were biologically active as shown in binding and cytotoxicity assays. These studies demonstrate the potential of PER.C6® cells for the production of high levels of functional recombinant IgM and other polymeric molecules, using a straightforward and rapid stable cell line generation method.

Authors

Anna Tchoudakova Corresponding author: atchoudakova@percivia.com

Percivia LLC

Frank Hensel

Patrys GmbH

Alec Murillo

Percivia LLC

Bernie Eng

Percivia LLC

Marketa Foley

Percivia LLC

Lakee Smith

Percivia LLC

Frank Schoenen

Patrys GmbH

Antonia Hildebrand

Patrys GmbH

Arndt-René Kelter

Patrys GmbH

Leodevico L. Ilag

Patrys Ltd.; University of Melbourne

H. Peter Vollmers

Universität Würzburg

Stephanie Brandlein

Universität Würzburg

Jane McIninch

Percivia LLC

John Chon

Percivia LLC

Gene Lee

Percivia LLC

Marco Cacciuttolo

Percivia LLC

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.