Methods for up-regulating antigen expression in tumors

Abstract

The invention provides methods of modulating tumor antigen associated (TAA) expression, and methods of modulating TAA expression in order to treat a tumor. More particularly, the invention provides methods of increasing an immune response against a tumor cell. Methods include administering to a subject with a tumor an amount of IFN-β receptor agonist and tumor associated antigen (TAA) sufficient to increase an immune response against the tumor cell.

1 - 65 . (canceled) 
     
     
         66 . A method of treating a tumor comprising administering to a subject with a tumor an amount of interferon-β (IFN-β) receptor agonist to up-regulate expression of a tumor associated antigen (TAA) on the tumor followed by administering an autologous immune cell that interacts with a tumor cell of the tumor, wherein the IFN-β receptor agonist comprises a polypeptide comprising the amino acid sequence of SEQ ID NO: 29 or SEQ ID NO: 30, thereby treating the tumor. 
     
     
         67 . The method of  claim 66 , wherein the immune cell is a lymphocyte. 
     
     
         68 . The method of  claim 67 , wherein the lymphocyte is a T lymphocyte. 
     
     
         69 . The method of  claim 66 , wherein the amino acid sequence of the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 29. 
     
     
         70 . The method of  claim 69 , wherein the amino acid sequence of the polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 29. 
     
     
         71 . The method of  claim 66 , wherein the amino acid sequence of the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 30. 
     
     
         72 . The method of  claim 71 , wherein the amino acid sequence of the polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 30. 
     
     
         73 . The method of  claim 66 , wherein the tumor is metastatic. 
     
     
         74 . The method of  claim 66 , wherein the treatment reduces tumor volume, inhibits an increase in tumor volume, stimulates tumor cell lysis or apoptosis, or reduces tumor metastasis. 
     
     
         75 . The method of  claim 66 , further comprising administering an anti-tumor therapy. 
     
     
         76 . The method of  claim 75 , wherein the anti-tumor therapy comprises surgical resection, radiotherapy, or chemotherapy. 
     
     
         77 . The method of  claim 66 , wherein the subject is human. 
     
     
         78 . The method of  claim 66 , wherein the TAA is selected from: Melan-A/MART-1, tyrosinase, gp100/pmel 17, TRP-1, TRP-2, an MITF, MITF-A, MITF-M, melanoma GP75, Annexin I, Annexin II, adenosine deaminase-binding protein (ADAbp), PGP 9.5, Colorectal associated antigen (CRC)—C017-1A/GA733, Ab2 BR3E4, CI17-1A/GA733, Hsp70, Hsp90, Hsp96, Hsp105, Hsp110, HSPPC-96, stress protein gp96 (a human colorectal cancer tumor rejection antigen, Heike 2000), gp96-associated cellular peptide, G250, Dipeptidyl peptidase IV (DPPIV), Mammaglobin, thyroglobulin, STn, Carcinoembryonic Antigen (CEA), Carcinoembryonic Antigen (CEA) epitope CAP-1, Carcinoembryonic Antigen (CEA) epitope CAP-2, etv6, aml1, Prostate Specific Antigen (PSA), PSA epitope PSA-1, PSA epitope PSA-2, PSA epitope PSA-3, Ad5-PSA, prostate-specific membrane antigen (PSMA), Prostatic Acid Phosphatase (PAP), Prostate epithelium-derived Ets transcription factor (PDEF), Parathyroid-hormone-related protein (PTH-rP), EGFR, PLU1, Oncofetal antigenimmature laminin receptor (OFA-iLR), MN/CA IX (CA9) (Shimizu, 2003), HP59, Cytochrome oxidase 1, sp100, msa, Ran GTPase activating protein, a RabGAP (Rab GTPase-activating) protein, PARIS-1, T-cell receptor/CD3-zeta chain, cTAGE-1, SCP-1, Glycolipid antigen-GM2, GD2 or GD3, GM3, FucosylGM1, Glycoprotein (mucin) antigens-Tn, Sialyl-Tn, TF and Mucin-1, CA125 (MUC-16), a MAGE family antigen, GAGE-1,2, BAGE, RAGE, LAGE-1, GnT-V, EPCAM/KSA, CDK4, a MUC family antigen, HER2/neu, ErbB-2/neu, p21 ras, RCAS1, α-fetoprotein, E-cadherin, α-catenin, β-catenin and γ-catenin, NeuGcGM3, Fos related antigen, Cyclophilin B, RCAS1, S2, L10a, L 10a, Telomerase rt peptide, cdc27, fodrin, p120ctn, PRAME, GA733/EoCam, NY-BR-1, NY-BR-2 NY-BR-3, NY-BR-4 NY-BR-5, NY-BR-6 NY-BR-7, NY-ESO-1, L19H1, MAZ, PINCH, PRAME, Prp1p/Zer1p, WT1, adenomatous polyposis coli protein (APC), PHF3, LAGE-1, SART3, SCP-1, SSX-1, SSX-2, SSX-4, TAG-72, TRAG-3, MBTAA, a Smad tumor antigen, lmp-1, HPV-16 E7, c-erbB-2, EBV-encoded nuclear antigen (EBNA)-1, Herpes simplex thymidine kinase (HSVtk), alternatively spliced isoform of XAGE-1 (L552S), TGF beta RII frame shift mutation, BAX frame shift mutation, or an antigenic fragment thereof. 
     
     
         79 . A method of treating a subject having or at risk of having a tumor comprising administering to the subject
 a) an amount of interferon-β (IFN-β receptor agonist that up-regulates expression of a tumor associated antigen (TAA) on the tumor and   b) the TAA,   wherein the TAA is administered singly or multiple times to the subject 1 day to 6 months before administering the IFN-β receptor agonist, and wherein the IFN-β receptor agonist comprises a polypeptide comprising the amino acid sequence of SEQ ID NO: 29 or SEQ ID NO: 30, thereby treating the subject.   
     
     
         80 . The method of  claim 79 , wherein the amino acid sequence of the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 29. 
     
     
         81 . The method of  claim 80 , wherein the amino acid sequence of the polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 29. 
     
     
         82 . The method of  claim 79 , wherein the amino acid sequence of the polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 30. 
     
     
         83 . The method of  claim 82 , wherein the amino acid sequence of the polypeptide consists of the amino acid sequence set forth in SEQ ID NO: 30. 
     
     
         84 . The method of  claim 79 , wherein the IFN-β receptor agonist is administered singly or multiple times. 
     
     
         85 . The method of  claim 79 , wherein the TAA is administered singly or multiple times to the subject 1 to 14 days before administering the IFN-β receptor agonist. 
     
     
         86 . The method of  claim 79 , wherein the TAA is administered singly or multiple times to the subject 14 to 30 days before administering the IFN-β receptor agonist. 
     
     
         87 . The method of  claim 79 , wherein the TAA is administered singly or multiple times to the subject 1 to 6 months before administering the IFN-β receptor agonist. 
     
     
         88 . The method of  claim 79 , wherein the tumor is metastatic. 
     
     
         89 . The method of  claim 79 , wherein the treatment reduces tumor volume, inhibits an increase in tumor volume, stimulates tumor cell lysis or apoptosis, or reduces tumor metastasis. 
     
     
         90 . The method of  claim 79 , wherein the treatment reduces one or more adverse symptoms associated with the tumor. 
     
     
         91 . The method of  claim 79 , wherein the treatment inhibits progression of the tumor. 
     
     
         92 . The method of  claim 79 , wherein the subject is a candidate for, is undergoing, or has undergone anti-tumor therapy. 
     
     
         93 . The method of  claim 92 , wherein the anti-tumor therapy comprises surgical resection, radiotherapy, or chemotherapy. 
     
     
         94 . The method of  claim 79 , further comprising administering an autologous immune cell that interacts with a cell of the tumor. 
     
     
         95 . The method of  claim 94 , wherein the immune cell is a lymphocyte. 
     
     
         96 . The method of  claim 95 , wherein the lymphocyte is a T lymphocyte. 
     
     
         97 . The method of  claim 79 , wherein the subject is human. 
     
     
         98 . The method of  claim 79 , wherein the TAA is selected from: Melan-A/MART-1, tyrosinase, gp100/pmel 17, TRP-1, TRP-2, an MITF, MITF-A, MITF-M, melanoma GP75, Annexin I, Annexin II, adenosine deaminase-binding protein (ADAbp), PGP 9.5, Colorectal associated antigen (CRC)—C017-1A/GA733, Ab2 BR3E4, CI17-1A/GA733, Hsp70, Hsp90, Hsp96, Hsp105, Hsp110, HSPPC-96, stress protein gp96 (a human colorectal cancer tumor rejection antigen, Heike 2000), gp96-associated cellular peptide, G250, Dipeptidyl peptidase IV (DPPIV), Mammaglobin, thyroglobulin, STn, Carcinoembryonic Antigen (CEA), Carcinoembryonic Antigen (CEA) epitope CAP-1, Carcinoembryonic Antigen (CEA) epitope CAP-2, etv6, aml1, Prostate Specific Antigen (PSA), PSA epitope PSA-1, PSA epitope PSA-2, PSA epitope PSA-3, Ad5-PSA, prostate-specific membrane antigen (PSMA), Prostatic Acid Phosphatase (PAP), Prostate epithelium-derived Ets transcription factor (PDEF), Parathyroid-hormone-related protein (PTH-rP), EGFR, PLU1, Oncofetal antigenimmature laminin receptor (OFA-iLR), MN/CA IX (CA9) (Shimizu, 2003), HP59, Cytochrome oxidase 1, sp100, msa, Ran GTPase activating protein, a RabGAP (Rab GTPase-activating) protein, PARIS-1, T-cell receptor/CD3-zeta chain, cTAGE-1, SCP-1, Glycolipid antigen-GM2, GD2 or GD3, GM3, FucosylGM1, Glycoprotein (mucin) antigens-Tn, Sialyl-Tn, TF and Mucin-1, CA125 (MUC-16), a MAGE family antigen, GAGE-1,2, BAGE, RAGE, LAGE-1, GnT-V, EPCAM/KSA, CDK4, a MUC family antigen, HER2/neu, ErbB-2/neu, p21ras, RCAS1, α-fetoprotein, E-cadherin, α-catenin, β-catenin and γ-catenin, NeuGcGM3, Fos related antigen, Cyclophilin B, RCAS1, S2, L10a, L10a, Telomerase rt peptide, cdc27, fodrin, p120ctn, PRAME, GA733/EoCam, NY-BR-1, NY-BR-2 NY-BR-3, NY-BR-4 NY-BR-5, NY-BR-6 NY-BR-7, NY-ESO-1, L19H1, MAZ, PINCH, PRAME, Prp1p/Zer1p, WT1, adenomatous polyposis coli protein (APC), PHF3, LAGE-1, SART3, SCP-1, SSX-1, SSX-2, SSX-4, TAG-72, TRAG-3, MBTAA, a Smad tumor antigen, lmp-1, HPV-16 E7, c-erbB-2, EBV-encoded nuclear antigen (EBNA)-1, Herpes simplex thymidine kinase (HSVtk), alternatively spliced isoform of XAGE-1 (L552S), TGF beta RII frame shift mutation, BAX frame shift mutation, or an antigenic fragment thereof.