Car receptor as a mediator of migratory cell chemotaxis and/or chemokinesis

Abstract

This invention relates to methods and compositions for modulating movement of eukaryotic cells with migratory capacity. More specifically, the invention relates to methods and compositions for modulating movement of CaR receptor expressing cells of hematopoietic, neural, epithelial, endothelial, or mesenchymal origin, in a specific site in a subject. The foregoing are useful, inter alia, in the treatment of conditions characterized by a need to modulate migratory-cell movement associated with specific sites in a subject. Specific sites include sites of inflammation and modulation of migratory-cell movement is movement away from an agent source, or repulsion. The invention also relates to methods for manipulating io hematopoeitic progenitor cells and related products. In particular the invention includes methods and products for using CaR receptor-related compositions to enhance mobilization of hematopoietic progenitor cells, to improve the efficiency of targeting cells to the bone marrow, and/or to modulate hematopoietic progenitor cell function.

1 .- 84 . (canceled) 
     
     
         85 . A method for enhancing bone marrow engraftment following bone marrow transplantation, comprising: contacting isolated bone marrow cells to be transplanted with a non-Ca ++  CaR receptor agonist in an effective amount to increase chemokine receptor expression in the isolated bone marrow cells to enhance bone marrow engraftment following bone marrow transplantation of said cells,
 wherein the non-Ca ++  CaR receptor agonist does not comprise NPS R-467. 
 
     
     
         86 . The method of  claim 85 , further comprising contacting the isolated bone marrow cells with Ca ++ . 
     
     
         87 . The method of  claim 85 , wherein the CaR receptor agonist is selected from the group consisting of CaR peptide and NPS S-467. 
     
     
         88 . The method of  claim 85 , wherein the CaR receptor agonist is CaR peptide. 
     
     
         89 . The method of  claim 85 , wherein the CaR receptor agonist is NPS S-467. 
     
     
         90 . The method of  claim 85 , wherein the isolated bone marrow cells comprise hematopoietic stem cells. 
     
     
         91 . The method of  claim 85 , wherein the isolated bone marrow cells comprise hematopoietic progenitor cells. 
     
     
         92 . The method of  claim 85 , wherein the chemokine receptor is the selected from the group consisting of CCR-2, CCR-5, and CXCR-4. 
     
     
         93 . The method of  claim 85 , wherein the chemokine receptor is CCR-2. 
     
     
         94 . The method of  claim 85 , wherein the chemokine receptor is CCR-5. 
     
     
         95 . The method of  claim 85 , wherein the chemokine receptor is CXCR-4. 
     
     
         96 . The method of  claim 85 , wherein the subject is human. 
     
     
         97 . The method of  claim 85 , wherein the subject has cancer. 
     
     
         98 . The method of  claim 97 , wherein the cancer is selected from the group consisting of: acute lymphocytic leukemia, acute myelogenous leukemia, multiple myeloma; AIDS associated leukemia, adult T-cell leukemia, adult T-cell lymphoma, Hodgkin's disease and lymphocytic lymphoma.