Abstract
Background: Interleukin-13 binds two receptors. The first is the IL-13Rα1/IL-4Rα heterodimer which also responds to IL-4 ligand engagement, is broadly expressed, and is canonically associated with type-2 immune signaling. The second, IL-13Rα2, also referred to as the IL-13 decoy receptor, is negligibly expressed in normal tissues but is overexpressed in a range of cancers including pancreatic, colorectal, and lung tumors. MDNA132 is an engineered IL-13 mutein with specificity for IL-13Rα2. Herein we characterize Bi-functional SuperKine ImmunoTherapies (“BiSKITs”) comprised of long-acting Fc-MDNA132 fusion constructs as proof-of-principle for targeted delivery of checkpoint inhibitors or IL-2 Superkines to IL-13Rα2-expressing tumors.
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