Anticalin® Proteins as Therapeutic Agents in Human Diseases

BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
Christine Rothe, A Skerra

Abstract

Anticalin proteins are an emerging class of clinical-stage biopharmaceuticals with high potential as an alternative to antibodies. Anticalin molecules are generated by combinatorial design from natural lipocalins, which are abundant plasma proteins in humans, and reveal a simple, compact fold dominated by a central β-barrel, supporting four structurally variable loops that form a binding site. Reshaping of this loop region results in Anticalin proteins that can recognize and tightly bind a wide range of medically relevant targets, from small molecules to peptides and proteins, as validated by X-ray structural analysis. Their robust format allows for modification in several ways, both as fusion proteins and by chemical conjugation, for example, to tune plasma half-life. Antagonistic Anticalin therapeutics have been developed for systemic administration (e.g., PRS-080: anti-hepcidin) or pulmonary delivery (e.g. PRS-060/AZD1402: anti-interleukin [IL]-4-Rα). Moreover, Anticalin proteins allow molecular formatting as bi- and even multispecific fusion proteins, especially in combination with antibodies that provide a second specificity. For example, PRS-343, which has recently entered clinical-stage development, combines an agonistic...Continue Reading

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Methods Mentioned

BETA
X-ray
phage
enzyme-linked immunosorbent assay
phage display
ELISA
fluorescence-activated cell sorting
xenografts

Clinical Trials Mentioned

NCT03325621
NCT03384290
NCT03330561

Software Mentioned

NGAL
PyMOL

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