Compositions comprising e-selectin antagonists and uses therefor

Abstract

This invention discloses the use of an E-selectin antagonist and a mobilizer of hematopoietic stem cells or progenitor cells in methods and compositions for treating or preventing immunocompromised conditions resulting from medical treatment. The present invention is particular relevant for prophylaxis and/or treatment of hematopoeitic disorders including neutropenia, agranulocytosis, anemia and thrombocytopenia in individuals receiving or proposed to receive treatments that target rapidly dividing cells or that disrupt the cell cycle or cell division.

1 .- 47 . (canceled) 
     
     
         48 . A composition comprising an E-selectin antagonist, wherein the E-selectin antagonist is not naturally occurring, and at least one mobilizer of hematopoietic stem cells or progenitor cells. 
     
     
         49 . The composition of  claim 48 , wherein the E-selectin antagonist is selected from the group consisting of an antigen binding molecule that is immuno-interactive with E-selectin, a peptide that binds to E-selectin and that blocks cell-cell adhesion, a carbohydrate mimetic of an E-selectin ligand, and a peptide mimetic of an E-selectin ligand. 
     
     
         50 . The composition of  claim 48 , wherein the E-selectin antagonist is a carbohydrate mimetic of an E-selectin ligand. 
     
     
         51 . The composition of  claim 48 , wherein the at least one mobilizer is selected from the group consisting of: AMD3100, interleukin-1 (IL-I), interleukin-3 (IL-3), interleukin-6 (IL-6), interleukin-11 (IL-11), interleukin-7 (IL-7), interleukin-8 (IL-8), interleukin-12 (IL 12), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF), stem cell factor, FLT-3 ligand, matrix metalloproteinase 2 (MMP2), MMP9, cathepsin G, elastase, cathepsin K, dipeptidyl peptidase-1, Mip-1α, Groβ, a small interfering RNA (siRNA) molecule specific for CXCL12, an antisense molecule specific for CXCL12, Fucoidan, and sulfated dextran. 
     
     
         52 . The composition of  claim 48 , wherein the at least one mobilizer is G-CSF. 
     
     
         53 . The composition of  claim 48 , wherein the E-selectin antagonist is a carbohydrate mimetic of an E-selectin ligand and the at least one mobilizer is G-CSF. 
     
     
         54 . The composition of  claim 48 , further comprising an agent that targets rapidly dividing cells and/or disrupts the cell cycle or cell division. 
     
     
         55 . The composition of  claim 54 , wherein the agent is a chemotherapeutic agent or a radiosensitizing agent. 
     
     
         56 . The composition of  claim 49 , further comprising an agent that targets rapidly dividing cells and/or disrupts the cell cycle or cell division. 
     
     
         57 . The composition of  claim 56 , wherein the agent is a chemotherapeutic agent or a radiosensitizing agent. 
     
     
         58 . The composition of  claim 50 , further comprising an agent that targets rapidly dividing cells and/or disrupts the cell cycle or cell division. 
     
     
         59 . The composition of  claim 58 , wherein the agent is a chemotherapeutic agent or a radiosensitizing agent. 
     
     
         60 . The composition of  claim 51 , further comprising an agent that targets rapidly dividing cells and/or disrupts the cell cycle or cell division. 
     
     
         61 . The composition of  claim 60 , wherein the agent is a chemotherapeutic agent or a radiosensitizing agent. 
     
     
         62 . The composition of  claim 48 , further comprising a medicament for treating an immunocompromised condition. 
     
     
         63 . The composition of  claim 62 , wherein the medicament is selected from the group consisting of an anemia medicament, a thrombocytopenia medicament, a neutropenia medicament, and an anti-infective agent. 
     
     
         64 . The composition of  claim 49 , further comprising a medicament for treating an immunocompromised condition. 
     
     
         65 . The composition of  claim 64 , wherein the medicament is selected from the group consisting of an anemia medicament, a thrombocytopenia medicament, a neutropenia medicament, and an anti-infective agent. 
     
     
         66 . The composition of  claim 50 , further comprising a medicament for treating an immunocompromised condition. 
     
     
         67 . The composition of  claim 66 , wherein the medicament is selected from the group consisting of an anemia medicament, a thrombocytopenia medicament, a neutropenia medicament, and an anti-infective agent. 
     
     
         68 . The composition of  claim 51 , further comprising a medicament for treating an immunocompromised condition. 
     
     
         69 . The composition of  claim 68 , wherein the medicament is selected from the group consisting of an anemia medicament, a thrombocytopenia medicament, a neutropenia medicament, and an anti-infective agent. 
     
     
         70 . The composition of  claim 48 , further comprising a pharmaceutically acceptable carrier.