Methods of modulating the negative chemotaxis of immune cells

Abstract

The current invention is directed to methods of inducing migration of an immune cell toward a cancer cell comprising inhibiting the activity of a chemorepellant released from the cancer cell.

1 - 20 . (canceled) 
     
     
         21 . A method for the treatment of cancer comprising inducing the migration of an immune cell toward a cancer cell by inhibiting the activity of a chemorepellant released from the cancer cell. 
     
     
         22 . The method of  claim 21 , wherein the cancer is selected from the group consisting of colon, prostate, breast, lung, skin, liver, bone, pancreas, ovary, testis, bladder, kidney, brain, head and neck cancer. 
     
     
         23 . The method of  claim 21 , wherein the activity of the chemorepellant is inhibited by the administration of a therapeutically effective amount of an agent that inhibits the activity of the chemorepellant. 
     
     
         24 . The method of  claim 23 , wherein the agent is an antibody that binds and inhibits the activity of the chemorepellant or is an antisense nucleic acid. 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . The method of  claim 21 , wherein the chemorepellant is selected from the group consisting of actin, 14-3-3 zeta/delta, apolipoprotein A1, hemopexin, PARK7, cofilin-1, 14-3-3 epsilon, 14-3-3-gamma, phosphoserine phosphatase, superoxide dismutase, profilin-2, beta-2 microglobulin, cytochrome C, cystatin B, macrophage migration inhibitory factor (MIF), FK506 binding protein, thioredoxin, galectin 3, human transferrin, human EF-1-gamma and human galectin 3 binding protein, or a biologically active fragment thereof. 
     
     
         28 . A method of inducing negative chemotaxis of a human migratory cell comprising administering an effective amount of a chemorepellant, wherein the chemorepellant comprises an amino acid sequence that has substantial identity to a protein isolated from ovarian cancer cystic fluid or from the supernatant of a cancer cell culture wherein the cancer cell is selected from the group consisting of a human renal adenocarcinoma cell line, a human renal carcinoma cell line, human glioblastoma cell line, human colon carcinoma cell line, human hepatocellular carcinoma cell line, human ovary clear carcinoma cell line and human prostate cancer cell line, or to a biologically active fragment of any of thereof, wherein the isolated protein or fragment is capable of inducing chemorepulsion of an immune cell. 
     
     
         29 . (canceled) 
     
     
         30 . The method of  claim 28 , wherein the chemorepellant is selected from the group consisting of actin, 14-3-3 zeta/delta, apolipoprotein A1, hemopexin, PARK7, cofilin-1, 14-3-3 epsilon, 14-3-3-gamma, phosphoserine phosphatase, superoxide dismutase, profilin-2, beta-2 microglobulin, cytochrome C, cystatin B, macrophage migration inhibitory factor (MIF), FK506 binding protein, thioredoxin, galectin 3, human transferrin, human EF-1-gamma and human galectin 3 binding protein, or a biologically active fragment of any of thereof. 
     
     
         31 . The method of  claim 28 , wherein the human migratory cell is an immune cell. 
     
     
         32 . The method of  claim 31 , wherein the immune cell is selected from the group consisting of lymphocytes, monocytes, neutrophils, eosinophils, mast cells, Natural killer cells, dendritic cells, and T cells. 
     
     
         33 . (canceled) 
     
     
         34 . A method of inhibiting the chemotactic induction of an immune cell in a patient in need thereof comprising administering to said patient a therapeutically effective amount of a chemorepellant wherein the chemorepellant comprises an amino acid sequence that has substantial identity to a protein isolated from ovarian cancer cystic fluid or from the supernatant of a cancer cell culture wherein the cancer cell is selected from the group consisting of a human renal adenocarcinoma cell line, a human renal carcinoma cell line, human glioblastoma cell line, human colon carcinoma cell line, human hepatocellular carcinoma cell line, human ovary clear carcinoma cell line and human prostate cancer cell line, or a biologically active fragment of any of thereof, wherein the isolated protein or fragment thereof is capable of inducing chemorepulsion of an immune cell. 
     
     
         35 . The method of  claim 34 , wherein the chemorepellant is selected from the group consisting of actin, 14-3-3 zeta/delta, apolipoprotein A1, hemopexin, PARK7, cofilin-1, 14-3-3 epsilon, 14-3-3-gamma, phosphoserine phosphatase, superoxide dismutase, profilin-2, beta-2 microglobulin, cytochrome C, cystatin B, macrophage migration inhibitory factor (MIF), FK506 binding protein, thioredoxin, galectin 3, human transferrin, human EF-1-gamma and human galectin 3 binding protein, or a biologically active fragment of any of thereof. 
     
     
         36 . The method of  claim 34 , wherein the patient is suffering from an inflammatory condition. 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 34 , wherein chemotaxis toward a medical implant is inhibited. 
     
     
         39 . The method of  claim 34 , wherein chemotaxis toward a transplant or graft is inhibited. 
     
     
         40 . The method of  claim 34 , wherein the chemorepellant is administered locally.