Origene_Jan2021_ProperAntibodyDesignKeeps - 22

Bispecific, Multispecific Antibodies Grapple with Cancer
that binds to CD3, a T-cell receptor (TCR), and

Fc-containing intact antibodies, allowing it to be

EpCAM, an adhesion molecule overexpressed in

removed easily and rapidly through the kidney.

80% of solid tumors.

Schellenberger's data suggests that AMX-268 may

" We give the drug in an inactive form and

have lower immunogenicity and a lower toxicity

convert it to the active form only when it is in the

profile among other potential EpCAM-targeting

tumor environment, " Schellenberger says. The

T-cell engagers such as Removab (Fresenius Biotech)

company's pro-drug is activated by the inflam-

and the investigational MT110 (Amgen).

matory process found primarily within the tumor
microenvironment, reducing off-target toxicity
and increasing antitumor selectivity, " so that if our

Moving from mono- to
bispecific antibodies

molecule finds that target in a healthy organ, it will

One company that is leveraging its success in

still leave it alone. "

developing monospecific antibodies into bi- and

The active form of the drug is smaller than typical

trispecific antibodies is Glycotope. According

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.

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Origene_Jan2021_ProperAntibodyDesignKeeps

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