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.
Claims8
A method of treating an individual for cancer, the method comprising administering an effective dose of a cell comprising (i) Granzyme B (GrB) fused to a truncated oncoprotein and an oncoprotein specific binding partner;
- and/or (ii) a nucleic acid encoding for Granzyme B (GrB) fused to a truncated oncoprotein and an oncoprotein specific binding partner;
- wherein the oncoprotein is human telomerase reverse transcriptase (hTERT), and the oncoprotein specific binding partner is an antibody, scFv or nanobody.
Dependencies are inferred from the claim text.