Origene_Jan2021_ProperAntibodyDesignKeeps - 23

Proper Antibody Design Keeps Specificity In Mind
to Anika Jäkel, PhD, the company's director of

product improvement as well as fast, reproducible,

preclinical pharmacology and cancer immunology,

and high-yield glycoprotein production. "

" Glycotope has strong expertise in glycobiology

" We do not use a standard platform approach

and focuses on the generation of antibodies against

for our bispecific programs, " Jäkel continues,

tumor-specific glycoepitopes. "

suggesting that by focusing on GlycoTargets, the

The company's first-in-class mAb, Gatipo-

company has positioned itself to screen several

tuzumab, targets the tumor-specific epitope

construct formats for each bispecific product idea.

TA-MUC1, a novel combined carbohydrate/peptide

" We can produce classical IgGs but also bispecific

conformational epitope on the tumor marker MUC1

formats in our GlycoExpress system, " she asserts.

(mucin-1). This antibody shows broad therapeutic

" We can test different glycosylation variants for

potential in 80-100% of its main solid tumor

identification of a lead candidate with highest

indicators (that is, ovarian, lung, and breast cancers).

antitumor efficacy. "

" Our most advanced pipeline bispecific is a

Although Glycotope is not exclusively focusing

TA-MUC1-targeting T-cell engager (PankoM-

on the bsAb market, Jäkel suggests that there

ab-CD3-GEX), " Jäkel points out. " It was designed

are many possible advantages to targeting

to combine the high tumor specificity of Gatipo-

two epitopes over monospecific antibodies,

tuzumab with activation of polyclonal T cells inde-

including increased specificity and/or avidity,

pendent of MHCI engagement upon simultaneous

increased inhibition of tumor growth, enhanced

binding of TA-MUC1 and CD3 on T cells. "

local tumor cell killing, and blockade of immune

A second molecule in development at Glycotope
is PankoMab-PDL-GEX, which combines binding
to TA-MUC1 with immune checkpoint molecule

checkpoint inhibitors.

Beyond bispecifics

PD-L1 attached to a glycol-optimized functional Fc

In immuno-oncology, a well-trod path is the

domain. PankoMab-PDL-GEX is designed to direct

redirection of tumor T cells. A less-well-traveled

checkpoint blockade to the tumor and thereby

path is being explored by Invenra, which seeks

enhance tumor cell killing.

to activate functional processes that require a

Glycotope's GlycoExpress (GEX®) technology
platform is used for screening and production of
biopharmaceuticals, such as those described above,

novel mechanism of action through bispecific and
higher-order antibody binding.
" A good example is agonist antibodies for the

and other glycoproteins for fully human optimized

tumor necrosis factor [TNF] receptor superfamily, "

glycosylation. " It consists of a toolbox of proprietary

says Bonnie Hammer, PhD, vice president of biologic

human cell lines generated by glycoengineering, "

development at Invenra. " The ligands for that family

says Jäkel. " It is biotechnologically optimized for

are trimeric. To get good activity, you need at least
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