Viral fusion protein treatment for ccr8 mediated diseases

Abstract

Compositions, methods, and kits are provided for treating CCR8 mediated diseases with applicability to atopic dermatitis and potential applicability to asthma, prurigo nodularis, nummular dermatitis, neurodermatitis, and lichen simplex chronicus and some lymphomas, multiple sclerosis, acquired immunodeficiency disease, peritoneal adhesions, Kaposi's sarcoma and atherogenesis—the expression of all of which, at least in part, is mediated by cells expressing the chemokine receptor CCR8. The compositions include proteins and fusion proteins from Molluscum contagiosum Virus (MCV) or variants, analogs and derivatives thereof which exhibit inhibitory activity. Examples of such MCV proteins are MC148 fusion protein (MC148fp) identified as MC148P-TAT-6xHis (“6xHis” disclosed as SEQ ID NO: 11), and its variants, fragments, analogs and derivatives which possess inhibitory activity. The variants, fragments, analogs and derivatives of MC148p and of MC148fp may be less than 100% homologous to MCV proteins as long as they are sufficiently homologous that inhibitory activity is preserved.

What is claimed is: 
     
         1 . A composition comprising a therapeutically effective amount of a fusion protein,
 wherein the fusion protein comprises a Molluscum contagiosum protein and a peptide,   wherein the Molluscum contagiosum protein confers at least one therapeutic activity to the fusion protein and   wherein the peptide comprises (a) three or more of lysine, histidine or arginine, (b) a TAT peptide or a combination of (a) and (b), and   wherein the peptide confers penetration of the fusion protein through the stratum corneum of skin.   
     
     
         2 . The composition of  claim 1 , wherein the therapeutic activity is selected from the group consisting of atopic dermatitis inhibitory activity, an atopic dermatitis-related atopic disease inhibitory activity, an allergic disease inhibitory activity, a Th2 mediated disorder inhibitory activity and a CCR8 mediated disorder inhibitory activity. 
     
     
         3 . The composition of  claim 1 , wherein the fusion protein is capable of penetrating the stratum corneum of human skin. 
     
     
         4 . The composition of  claim 3 , wherein the penetration by the fusion is enhanced as compared the Molluscum contagiosum protein alone. 
     
     
         5 . The composition of  claim 1 , wherein the peptide comprises SEQ ID No. 12. 
     
     
         6 . The composition of  claim 1 , wherein the peptide comprises between 3 and 20 histidine residues. 
     
     
         7 . The composition of  claim 1 , wherein the peptide is selected from the group consisting of SEQ ID Nos. 9, 10 and 11. 
     
     
         8 . The composition of  claim 1 , wherein the peptide is fused at the C-terminus of the Molluscum contagiosum protein. 
     
     
         9 . The composition of  claim 1 , wherein the peptide is fused at the N-terminus of the Molluscum contagiosum protein. 
     
     
         10 . The composition of  claim 1 , wherein the peptide comprises a TAT sequence and a poly-histidine sequence. 
     
     
         11 . The composition of  claim 1 , wherein the Molluscum contagiosum protein comprises MC148p1, MC148p2 or MC148p3. 
     
     
         12 . The composition of  claim 1 , wherein the Molluscum contagiosum protein comprises SEQ ID No.2, SEQ ID No. 4 or an amino acid sequencing have at least 86% homology to SEQ ID No. 2. 
     
     
         13 . The composition of  claim 1 , wherein the Molluscum contagiosum protein comprises an identical amino acid sequence at positions corresponding to amino acids 25-29 of SEQ ID No.2 or SEQ ID No. 4. 
     
     
         14 . A method of treating skin-related condition or disease, comprising administering the composition of  claim 1 . 
     
     
         15 . The method of  claim 14 , wherein the skin-related condition is selected from the group consisting of atopic dermatitis, an allergic condition, a Th2 mediated disorder and a CCR8-mediated disorder. 
     
     
         16 . The method of  claim 15 , wherein the Molluscum contagiosum protein comprises MC148p1, MC148p2 or MC148p3. 
     
     
         17 . The method of  claim 16 , wherein the peptide comprises a TAT sequence and a poly-histidine sequence. 
     
     
         18 . The method of  claim 16 , wherein the peptide is selected from the group consisting of SEQ ID Nos. 9, 10 and 11.