US2014271683A1PendingUtilityA1

Therapeutic and Diagnostic Methods for Manipulating Phagocytosis Through Calreticulin and Low Density Lipoprotein-Related Receptor

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Individually held — no corporate assignee on recordPriority: Dec 21, 2010Filed: Dec 21, 2011Published: Sep 18, 2014
Est. expiryDec 21, 2030(~4.4 yrs left)· nominal 20-yr term from priority
Inventors:Mark P. ChaoRachel Weissman-TsukamotoSiddhartha JaiswalRavindra MajetiIrving L. Weissman
G01N 33/5759G01N 33/57595C07K 16/2803C07K 14/435G01N 2333/4722C07K 16/2896G01N 2800/52C07K 2317/73A61K 2039/505G01N 33/56966C07K 2317/76G01N 2333/47G01N 33/6872A61K 39/3955C12Q 1/6886A61K 35/28G01N 33/57492
49
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Claims

Abstract

Therapeutic and diagnostic methods are provided, which methods relate to the expression of calreticulin on cancer cells and hematopoietic cells.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of targeting or depleting cancer cells, the method comprising:
 contacting cancer cells with an agent that specifically binds calreticulin in order to target or deplete the cells.   
     
     
         2 . The method of  claim 1 , wherein the cancer cells are contacted prior to treatment with a chemotherapeutic agent. 
     
     
         3 . The method of  claim 1 , wherein cancer stem cells are specifically targeted. 
     
     
         4 . The method of  claim 1 , wherein the cancer cells are leukemia cells. 
     
     
         5 . The method  claim 4 , wherein the cells are selected from AML, CML, ALL and NHL. 
     
     
         6 . The method of  claim 1 , wherein the cancer cells are carcinoma cells. 
     
     
         7 . The method of  claim 6 , wherein the carcinoma is a squamous cell carcinoma or an ovarian carcinoma. 
     
     
         8 . The method of  claim 1 , wherein the agent is an antibody. 
     
     
         9 . The method of  claim 8 , wherein said antibody is conjugated to a cytotoxic agent. 
     
     
         10 . The method of  claim 8 , wherein the antibody is conjugated to a detectable label for imaging. 
     
     
         11 . The method of  claim 8 , wherein the antibody is a bispecific antibody. 
     
     
         12 . The method of  claim 11 , wherein the bispecific antibody binds to calreticulin and CD47. 
     
     
         13 . The method of  claim 1 , wherein the agent is an agonist of calreticulin-mediated phagocytosis. 
     
     
         14 . A method of protecting blood cells from phagocytosis, the method comprising:
 contacting said cells with a calreticulin blocking agent.   
     
     
         15 . The method of  claim 14 , wherein the blocking agent is a CRT blocking peptide. 
     
     
         16 . The method of  claim 14 , wherein the blocking agent is a CRT blocking oligosaccharide. 
     
     
         17 . The method of  claim 14 , wherein the blocking agent is a CRT blocking antibody. 
     
     
         18 . The method of  claim 14 , wherein said depleting is performed on said blood cells ex vivo. 
     
     
         19 . The method of  claim 14 , comprising:
 administering to an individual a composition comprising a population of hematopoietic cells and a calreticulin blocking agent that down-regulates phagocytosis.   
     
     
         20 . The method of  claim 19 , wherein said cells are hematopoietic stem cells. 
     
     
         21 . The method of  claim 19 , wherein said cells are hematopoietic progenitor cells. 
     
     
         22 . A method of determining the fraction of normal cells susceptible to anti-CD47 based therapies through expression of calreticulin, so that minimal potential toxicity to the patient will result. 
     
     
         23 . The method of  claim 22 , wherein said cells are hematopoietic stem and/or progenitor cells. 
     
     
         24 . The method of  claim 22  wherein said cells are blood cells and/or platelets. 
     
     
         25 . The method of  claim 22  wherein said cells are tissue stem and/or progenitor cells detected in tissue biopsies, including intestinal crypt cells, lung cells.

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