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US 2022/0267752 A1Published application
Cell-targeted cytotoxic constructs
AssigneeResearch Development Foundation
InventorsXinjian LIN, Xiying SHANG, Stephen B. HOWELL
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Abstract
Cell-targeted cytotoxic agents, including sortase serine protease constructs, are provided. Such compounds can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer). In some aspects, recombinant sortase serine proteases, such as Granzyme B polypeptides, are provided that exhibit improved stability and cell toxicity.
Claims11
-76. (canceled)
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 5 and 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;
- wherein the targeting moiety is bound to the N-terminus of the linking polypeptide and the cytotoxic moiety is bound to the C-terminus of the linking polypeptide.
2 more elements
Dependencies are inferred from the claim text.