US2007128159A1PendingUtilityA1

Chemokines as adjuvants of immune response

63
Assignee: SCHERING CORPPriority: Jul 16, 1998Filed: Jan 24, 2007Published: Jun 7, 2007
Est. expiryJul 16, 2018(expired)· nominal 20-yr term from priority
Inventors:Alain VicariChristophe CauxDrake Laface
A61K 2039/55522A61K 38/195A61K 38/193A61K 38/2026A61K 38/191A61K 2039/53A61K 38/1709A61K 39/001194A61K 39/001191A61K 39/001186A61K 39/001181A61K 39/001156A61K 39/00119A61K 39/00117A61K 39/001157
63
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Claims

Abstract

Dendritc cells play a critical role in antigen-specific immune responses. Materials and methods are provided for treating disease states, including cancer and autoimmune disease, by facilitating or inhibiting the migration or activation of antigen-presenting dendritic cells. In particular, chemokines are used to initiate, amplify or modulate an immune response. In one embodiment, chemokines are used to attract dentritic cells to the site of antigen delivery. An increase number of dendritic at the site of antigen delivery means more antigen uptake and a modified immune response.

Claims

exact text as granted — not AI-modified
1 . The use of a chemokine capable of directing the migration of dendritic cells in the manufacture of a medicament for the treatment of a disease state.  
     
     
         2 . The use of  claim 1  wherein the chemokine is selected from the group consisting of MCP-1, MCP-2, MCP-3, MCP-4, MIP-1α, MIP-1β, MIP-3α, RANTES, SDF-1, Teck, DCtactin-β, 6Ckine/SLC, LEC, MDC, and MIP-5.  
     
     
         3 . The use of  claim 1  wherein the chemokine is capable of directing the migration of dendritic cells to the site of antigen delivery.  
     
     
         4 . The use of  claim 1  wherein the chemokine is capable of directing the migration of dendritic cells to lymphoid organs.  
     
     
         5 . The use of  claim 1  wherein the disease state is a bacterial infection, a viral infection, a fungal infection, a parasitic infection or cancer.  
     
     
         6 . The use of  claim 1  wherein the disease state is an autoimmune disease, tissue rejection or an allergy.  
     
     
         7 . The use of  claim 5  wherein the disease state is cancer selected from the group consisting of melanoma, breast, pancreatic, colon, lung, glioma, hepatocellular, endometrial, gastric, intestinal, renal, prostate, thyroid. ovarian, testicular, liver, head and neck, colorectal, esophagus, stomach, eye, bladder, glioblastoma, and metastatic carcinomas.  
     
     
         8 . The use of  claim 3  wherein the dendritic cells are immature dendritic cells.  
     
     
         9 . The use of  claim 8  wherein the chemokine is selected from the group consisting of MCP-1, MCP-2, MCP-3, MCP-4, MIP-1B, MDC, MIP-3α, MIP-1α, RANTES and MIP-5.  
     
     
         10 . The use of  claim 4  wherein the chemokine is MIP-3β.  
     
     
         11 . The use of  claim 3  further comprising the use of at least one disease associated antigen.  
     
     
         12 . The use of  claim 11  wherein the antigen is a tumor-associated antigen.  
     
     
         13 . The use of  claim 11  wherein the antigen is a bacterial, viral or fungal antigen.  
     
     
         14 . The use of  claim 12  wherein the tumor-associated antigen is selected from the group consisting of Melan-A, tyrosinase, p97, β-HCG, GalNAc, MAGE-1, MAGE-2, MAGE-3, MAGE-4, MAGE-12, MART-1, MUC1, MUC2, MUC3, MUC4, MUC18, CEA, DDC, melanoma antigen gp75, Hker 8, high molecular weight melanoma antigen, K19, Tyr1 and Tyr2, members of the pMel 17 gene family, c-Met, PSA, PSM, α-fetoprotein, thyroperoxidase, gp100, NY-ESO-1, telomerase and p53.  
     
     
         15 . The use of  claim 14  wherein the cancer is prostate cancer and the tumor-associated antigen is PSA and/or PSM.  
     
     
         16 . The use of  claim 14  wherein the disease state is melanoma and the tumor-associated antigen is Melan-A, gp 100 or tyrosinase.  
     
     
         17 . The use of  claim 1  further comprising the use of an activating agent.  
     
     
         18 . The use of  claim 15  wherein the activating agent is selected from TNFα, RP-105, an anti-CD-40 antibody and nucleic acids containing unmethylated CpG motifs or ligands of toll-like receptors.  
     
     
         19 . The use of  claim 1  further comprising the use of a combination of GM-CSF and IL-4 in conjunction with the chemokine.  
     
     
         20 . The use of  claim 1  wherein the chemokines are administered intradermally, intramuscularly, subcutaneously, topically, or in the form of a vector.  
     
     
         21 . A method of enhancing an immune response in a mammal comprising administering chemokine MCP-4 or a biologically active fraction of chemokine MCP-4 to said mammal.  
     
     
         22 . The method of  claim 21  wherein said chemokine is recombinant.  
     
     
         23 . The method of  claim 21  wherein said chemokine is human.  
     
     
         24 . The method of  claim 21  further comprising administering a substance which allows for the slow release of said chemokine at a delivery site.  
     
     
         25 . The method of  claim 21  further comprising administering an antigen with said chemokine.  
     
     
         26 . The method of  claim 25  wherein a fusion protein comprising MCP-4 and antigen is administered to said mammal.  
     
     
         27 . The method of  claim 25  wherein said antigen is a tumor associated antigen.  
     
     
         28 . The method of  claim 26  wherein said antigen is a tumor associated antigen.  
     
     
         29 . The method of  claim 25  wherein said antigen is a bacterial, viral or fungal antigen.  
     
     
         30 . The method of  claim 26  wherein said antigen is a bacterial viral or fungal antigen.  
     
     
         31 . The method of  claim 25  wherein said tumor associated antigen is selected from the group consisting of Melan-A, tyrosinase, p97, β-HCG, GalNAc., MAGE-1, MAGE-2, MAGE-3, MAGE-4, MAGE-12, MART-1, MUC1, MUC2, MUC3, MUC4, MUC18, CEA, DDC, melanoma antigen gp75, Hker 8, high molecular weight melanoma antigen, K19, Tyr1 and Tyr2, members of the pMel 17 gene family, c-Met, PSA, PSM, α-fetoprotein, thyroperoxidase, gp 100, p53 and telomerase.  
     
     
         32 . The method of  claim 26  wherein said tumor associated antigen is selected from the group consisting of Melan-A, tyrosinase, p97, β-HCG, GalNAc., MAGE-1, MAGE-2, MAGE-3, MAGE-4, MAGE-12, MART-1, MUC1, MUC2, MUC3, MUC4, MUC18, CEA, DDC, melanoma antigen gp75, Hker 8, high molecular weight melanoma antigen, K19, Tyr1 and Tyr2, members of the pMel 17 gene family, c-Met, PSA, PSM, α-fetoprotein, thyroperoxidase, gp 100, p53 and telomerase.  
     
     
         33 . The method of  claim 25  further comprising administering a combination of GM-CSF and IL-4.  
     
     
         34 . The method of  claim 26  further comprising administering a combination of GM-CSF and IL-4.  
     
     
         35 . The method of  claim 21  further comprising administering an activating agent with said chemokine.  
     
     
         36 . The method of  claim 21  wherein said chemokine is administered intradermally, intramuscularly, subcutaneously, topically, or in the form of a vector.  
     
     
         37 . A fusion protein comprising MCP-4 and antigen.  
     
     
         38 . The fusion protein of  claim 37  wherein said antigen is a tumor associated antigen.  
     
     
         39 . The fusion protein of  claim 38  wherein said tumor associated antigen is selected from the group consisting of Melan-A, tyrosinase, p97, β-HCG, GalNAc., MAGE-1, MAGE-2, MAGE-3, MAGE4, MAGE-12, MART-1, MUC1, MUC2, MUC3, MUC4, MUC18, CEA, DDC, melanoma antigen gp75, Hker 8, high molecular weight melanoma antigen, K19, Tyr1 and Tyr2, members of the pMel 17 gene family, c-Met, PSA, PSM, α-fetoprotein, thyroperoxidase, gp 100, p53 and telomerase.  
     
     
         40 . The fusion protein of  claim 38  wherein said antigen is a bacterial, viral or fungal antigen.  
     
     
         41 . A plasmid comprising the fusion protein of  claim 37 .  
     
     
         42 . The plasmid of  claim 39  further comprising a promoter sequence particularly suited for dendritic cells.  
     
     
         43 . A viral vector comprising the fusion protein of  claim 37 .  
     
     
         44 . A method of enhancing an immune response in a mammal comprising administering chemokine 6Ckine or a biologically active fraction of chemokine 6Ckine to said mammal.  
     
     
         45 . The method of  claim 44  wherein said chemokine is recombinant.  
     
     
         46 . The method of  claim 44  wherein said chemokine is human.  
     
     
         47 . The method of  claim 44  further comprising administering a substance which allows for the slow release of said chemokine at a delivery site.  
     
     
         48 . The method of  claim 44  further comprising administering an antigen with said chemokine.  
     
     
         49 . The method of  claim 48  wherein a fusion protein comprising 6Ckine and antigen is administered to said mammal.  
     
     
         50 . The method of  claim 48  wherein said antigen is a tumor associated antigen.  
     
     
         51 . The method of  claim 49  wherein said antigen is a tumor associated antigen.  
     
     
         52 . The method of  claim 48  wherein said antigen is a bacterial, viral or fungal antigen.  
     
     
         53 . The method of  claim 49  wherein said antigen is a bacterial viral or fungal antigen.  
     
     
         54 . The method of  claim 48  wherein said tumor associated antigen is selected from the group consisting of Melan-A, tyrosinase, p97, β-HCG, GalNAc., MAGE-1, MAGE-2, MAGE-3, MAGE-4, MAGE-12, MART-1, MUC1, MUC2, MUC3, MUC4, MUC18, CEA, DDC, melanoma antigen gp75, Hker 8, high molecular weight melanoma antigen, K19, Tyr1 and Tyr2, members of the pMel 17 gene family, c-Met, PSA, PSM, α-fetoprotein, thyroperoxidase, gp 100, p53 and telomerase and C26 colon carcinoma.  
     
     
         55 . The method of  claim 49  wherein said tumor associated antigen is selected from the group consisting of Melan-A, tyrosinase, p97, β-HCG, GalNAc, MAGE-1, MAGE-2, MAGE-3, MAGE-4, MAGE-12, MART-E, MUC1, MUC2, MUC3, MUC4, MUC18, CEA, DDC, melanoma antigen gp75, Hker 8, high molecular weight melanoma antigen, K19, Tyr1 and Tyr2, members of the pMel 17 gene family, c-Met, PSA, PSM, α-fetoprotein, thyroperoxidase, gp 100, p53 and telomerase and C26 colon carcinoma.  
     
     
         56 . The method of  claim 48  further comprising administering a combination of GM-CSF and IL-4.  
     
     
         57 . The method of  claim 49  further comprising administering a combination of GM-CSF and IL-4.  
     
     
         58 . The method of  claim 44  further comprising administering an activating agent with said chemokine.  
     
     
         59 . The method of  claim 44  wherein said chemokine is administered intradermally, intramuscularly, subcutaneously, topically, or in the form of a vector.  
     
     
         60 . A fusion protein comprising 6Ckine and antigen.  
     
     
         61 . The fusion protein of  claim 60  wherein said antigen is a tumor associated antigen.  
     
     
         62 . The fusion protein of  claim 61  wherein said tumor associated antigen is selected from the group consisting of Melan-A, tyrosinase, p97, β-HCG, GalNAc., MAGE-1, MAGE-2, MAGE-3, MAGE-4, MAGE-12, MART-1, MUC1, MUC2, MUC3, MUC4, MUC18, CEA, DDC, melanoma antigen gp75, Hker 8, high molecular weight melanoma antigen, K19, Tyr1 and Tyr2, members of the pMel 17 gene family, c-Met, PSA, PSM, α-fetoprotein, thyroperoxidase, gp 100, p53 and telomerase.  
     
     
         63 . The fusion protein of  claim 61  wherein said antigen is a bacterial, viral or fungal antigen.  
     
     
         64 . A plasmid comprising the fusion protein of  claim 60 .  
     
     
         65 . The plasmid of  claim 62  further comprising a promoter sequence particularly suited for dendritic cells.  
     
     
         66 . A viral vector comprising the fusion protein of  claim 60.

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