Compositions and methods for the inhibition of cripto / grp78 complex formation and signaling
AssigneeResearch Development Foundation
InventorsPeter C. Gray, Gidi Shani, Jonathan A. Kelber, Wylie Vale
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Abstract
The present invention provides methods compositions and methods for treating a hyperproliferative disease comprising disrupting Cripto/GRP78 complex formation in a hyperproliferative cell. In certain embodiments, an antibody and/or siRNA may be used to inhibit Cripto/GRP78 binding, optionally coupled with other cancer therapies. Also provided are methods for identifying therapeutic compounds which can selectively inhibit Cripto/GRP78 binding.
Claims29
A method for inhibiting Cripto signaling in a cell to reduce the cell's proliferation comprising contacting the cell with an amount of a selective GRP78/Cripto targeting compound that is effective to inhibit the formation of complexes between Cripto and GRP78 to thereby reduce the cell's proliferation.
A method of screening for an inhibitor of Cripto/GRP78 complex formation comprising:
- a) obtaining a candidate modulator;
- b) contacting the candidate modulator with a Cripto and a GRP78;
- and
- c) measuring the formation of Cripto/GRP78 complexes;
- wherein decrease in the formation of Cripto/GRP78 complexes or a decrease in Cripto/GRP78 complex signaling in the presence of the candidate modulator indicates that the candidate modulator is an inhibitor of Cripto/GRP78 complex formation.
A humanized monoclonal anti-GRP78 antibody, wherein the antibody binds an N-20 epitope in GRP78, and wherein said binding inhibits the formation of Cripto/GRP78 complexes.
Dependencies are inferred from the claim text.