Activated cytokine polypeptides and methods of their use

Abstract

FIELD: biotechnology.SUBSTANCE: recombinant fusion proteins that are conditionally active variants of a cytokine, used in medicine in antitumor therapy. Fusion proteins containing a functional cytokine polypeptide have reduced or minimal ability to activate the cytokine receptor. Once activated by cleavage of the linker that connects the blocking fragment in sequence to the active cytokine, the cytokine can bind to its receptor and signal. The fusion proteins also contain an element to extend half-life in vivo, which is cleaved from the cytokine in the tumor microenvironment.EFFECT: conditionally active cytokine prodrug with an extended half-life that delivers the active cytokine after cleavage by a protease to desired sites of activity, such as the tumor microenvironment.13 cl, 41 dwg, 3 tbl, 28 ex

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