Potelligent CHOK1SV cell line is a combination of BioWa’s Potelligent glycosylation technology and Lonza’s GS Gene Expression System, which uses Lonza’s host cell line CHOK1SV.
Lonza said the combined technology is “designed to improve the potency and efficacy of therapeutic antibodies by enhancing antibody-dependent cellular cytotoxicity (ADCC), one of the major mechanisms of therapeutic antibodies.”
ArGEN-X will use the tech to develop ARGX-110, a monoclonal antibody in its pipeline which targets CD70 positive tumours. It works in three ways: cancer cell depletion via ADCC, and deprivation of both a key stimulation signal and immune privilege.
Double gene knock out
Karen Fallen, VP of Licensing and Technology at Lonza, told Biopharma-Reporter.com Lonza’s host cell line is “pre-adapted to growth in chemically defined, animal component-free (CDACF) media and suspension culture. Its pre-adaptation to suspension culture aids adaptation of GS cell lines back to growth in suspension culture after transfection.”
Under the agreement, this host cell line is used to produce the high-ADCC mAbs created by BioWa’s technology.
“Scientists at Kyowa Hakko Kogyo Co. Ltd (now Kyowa Hakko Kirin) demonstrated that an antibody with a reduced fucose content in glycan moieties exhibited much higher antibody dependent cellular cytotoxicity (ADCC) activity compared to a normally fucosylated antibody,” said Fallen.
“They confirmed that the mechanism behind the enhanced ADCC of a low/no-fucose antibody was its increased affinity to FcγRIIIa (CD16), the major Fc receptor for ADCC in humans.
“A cell line with knockout of both alleles for the gene responsible for fucose addition (α1,6-fucosyltransferase; FUT8) can take advantage of this phenomenon, producing Potelligent mAbs with enhanced ADCC activity.”
Pfizer and AstraZeneca deals
The result of the collaboration, she said, was an FUT8 double gene knock out variant of CHOK1SV, developed for therapeutic protein expression.
This is the third disclosed license agreement for Potelligent and CHOK1SV, following deals with AstraZeneca in December and Pfizer in July 2013.
BioWa has licensed its Potelligent technology to arGEN-X since 2010, and the addition of Lonza’s cell line this week makes this a tripartite agreement.
ArGEN-X uses llama antibodies for its discovery platform rather than transgenic mice, the industry standard. Llamas are outbred and therefore have no blind spots in their immune systems.