Cytotoxic molecules responsive to intracellular ligands for selective T cell mediated killing
AssigneeThe Regents of the University of California
InventorsYvonne Y. Chen, Patrick Ho
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Abstract
Compositions and methods are provided for the cell-mediated targeted killing of diseased cells based on the presence of an intracellular antigen, rather than a surface-bound marker. The targeting cells are modified to express a cytotoxic protein that is delivered into a targeted cell, and after delivery is selectively activated by the presence of a cytoplasmic protein of interest. In one embodiment of the invention, the cytotoxic molecule is a Granzyme B (GrB) polypeptide. In the compositions of the invention, GrB is modified to render its cytotoxic enzymatic functions inactive, until the presence of an intracellular antigen unlocks the GrB molecule to enable enzymatic activities.
Claims12
A fusion protein comprising GrB and an oncoprotein specific binding partner fused internal to GrB.
A T cell comprising a fusion protein, wherein the fusion protein comprises mature Granzyme B (GrB) having a cancer-associated protease cleavage site at the N-terminus of GrB.
Dependencies are inferred from the claim text.