Sartorius #2 eBook - 2019 - 9

Importance of mAb Discovery and Development in Immunotherapy

Moving from mono- to bispecific antibodies
One company that is leveraging its success in developing monospecific antibodies
into bi- and trispecific antibodies is Glycotope. According to Anika Jäkel, PhD, the
company's director of preclinical pharmacology and cancer immunology, "Glycotope
has strong expertise in glycobiology and focuses on the generation of antibodies
against tumor-specific glycoepitopes."
The company's first-in-class mAb, Gatipotuzumab, targets the tumor-specific epitope
TA-MUC1, a novel combined carbohydrate/peptide conformational epitope on the
tumor marker MUC1 (mucin-1). This antibody shows broad therapeutic potential in
80-100% of its main solid tumor indicators (that is, ovarian, lung, and breast cancers).
"Our most advanced pipeline bispecific is a TA-MUC1-targeting T-cell engager
(PankoMab-CD3-GEX)," Jäkel points out. "It was designed to combine the high tumor
specificity of Gatipotuzumab with activation of polyclonal T cells independent of
MHCI engagement upon simultaneous binding of TA-MUC1 and CD3 on T cells."
A second molecule in development at Glycotope is PankoMab-PDL-GEX, which
combines binding to TA-MUC1 with immune checkpoint molecule PD-L1 attached to
a glycol-optimized functional Fc domain. PankoMab-PDL-GEX is designed to direct
checkpoint blockade to the tumor and thereby enhance tumor cell killing.
Glycotope's GlycoExpress (GEX®) technology platform is used for screening and
production of biopharmaceuticals, such as those described above, and other glycoproteins for fully human optimized glycosylation. "It consists of a toolbox of proprietary
human cell lines generated by glycoengineering," says Jäkel. "It is biotechnologically
optimized for product improvement as well as fast, reproducible, and high-yield
glycoprotein production."

9 |

GENengnews.com

Aberrant glycosylation patterns specific to cancer cells can be targeted by engineered
antibodies, such as those developed by Glycotope using its GlycoExpress (GEX) platform. For
example, the company's PankoMab-GEX antibody recognizes a tumor-specific epitope of
MUC1 (TA-MUC1). Left: Schematic illustration of MUC1 highlighting the PDTRP motif, which
has a conformational epitope induced by the carbohydrate antigens Tn or TF. Upper right:
Normal ovarian tissue, which lacks PankoMab-GEX staining. Lower right: Ovarian carcinoma
detected with PankoMab-GEX, which can recruit the immune system to destroy tumor cells
http://www.GENengnews.com
Sartorius #2 eBook - 2019

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