Dodekin is a single-chain polypeptide consisting of the two subunits of the immunomodulatory payload IL12 fused to a human vascular targeting antibody in tandem diabody format. This novel format greatly improves the process development characteristics of immunocytokines containing multi-subunit cytokine payloads. IL12 has potent anti-cancer activity but its use as a therapeutic protein is limited by associated toxicities, by selectively delivering IL12 to the sub-endothelial extracellular matrix in tumor blood vessels it is possible to drastically improve the therapeutic index of this cytokine.
Quantitative biodistribution studies on Dodekin have shown preferential tumor uptake of the molecule compared to healthy organs and our pre-clinical work shows that the immunocytokine has a potent anti-tumor activity in several immunocompetent murine models of cancer. Dodekin is also able to induce long-lasting tumor eradication when administered in combination with paclitaxel, and potentiates the action of other therapeutic agents such immunological checkpoint inhibitors and immunocytokines, particularly those based around IL2, TNF or IL4. The product exhibits potent activity against subcutaneous, metastatic and orthotopic tumors.
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