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US 11,913,043 B2Granted
Cell-targeted cytotoxic constructs
AssigneeResearch Development Foundation
InventorsXinjian Lin, Xiying Shang, Stephen B. Howell
Life of this patent
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Abstract
The invention is directed to cell-targeted cytotoxic agents, including sortase serine protease constructs. Methods for targeted cell killing for treatment of proliferative diseases, for example, cancer, are provided. Exemplary embodiments comprise an R-spondin ligand for targeting the cytotoxic agents to effect the cell killing.
Claims15
A cell-targeted cytotoxic construct comprising:
- (a) a targeting moiety that is an R-spondin targeting ligand that comprises two-tandem furin-like cysteine-rich (Fu-CRD) R-spondin domains, wherein the R-spondin targeting polypeptide ligand binds to a cell surface human LGR 4, LGR 5 and/or LGR 6 receptors;
- (b) a linking polypeptide that comprises a sortase recognition site, the linking polypeptide being positioned between the targeting moiety and the cytotoxic moiety;
- and
- (c) a cytotoxic moiety that comprises a toxin or chemotherapeutic, wherein the linking polypeptide is positioned between the targeting moiety and the cytotoxic moiety, and wherein the linking polypeptide comprises LPETG (SEQ ID NO:
- 66).
2 more elements
Dependencies are inferred from the claim text.