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AssigneeWerewolf Therapeutics, Inc.
InventorsWilliam Winston, Heather Brodkin, Cynthia Seidel-Dugan, Daniel Hicklin, Jose Andres Salmeron-Garcia
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The disclosure features fusion proteins that are conditionally active variants of a cytokine of interest. In one aspect, the full-length polypeptides of the invention have reduced or minimal cytokine-receptor activating activity even though they contain a functional cytokine polypeptide. Upon activation, e.g., by cleavage of a linker that joins a blocking moiety, e.g. a steric blocking polypeptide, in sequence to the active cytokine, the cytokine can bind its receptor and effect signaling. Typically, the fusion proteins further comprise an in vivo half-life extension element, which may be cleaved from the cytokine in the tumor microenvironment.
A conditionally active IL-18 comprising a fusion polypeptide comprising
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