Peptide epitopes of VEGFR-2/KDR that inhibit angiogenesis

Abstract

The disclosure provides antigenic peptides of Vascular Endothelial Growth Factor Receptor 2(VEGFR-2)/KDR. Pharmaceutical compositions including the peptides and/or antigen presenting cells that exhibit the VEGFR-2/KDR peptides on their cell surface are also provided. Methods for eliciting an immune response and for inhibiting angiogenesis by administering such pharmaceutical compositions are provided.

1 . An isolated or synthetic peptide that binds to a Major Histocompatibility (MHC) Class I molecule comprising a subsequence of a Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2).  
     
     
         2 . The peptide of  claim 1 , wherein the peptide consists of between 8 and 12 amino acids.  
     
     
         3 . The peptide of  claim 1 , wherein the peptide consists of 9 or 10 amino acids.  
     
     
         4 . The peptide of  claim 1 , wherein the peptide is a subsequence of a murine VEGFR-2 comprising the sequence TNXI, where X is any amino acid.  
     
     
         5 . The peptide of  claim 4 , wherein the peptide comprises: 
 (a) the sequence VILTNPISM or FSNSTNDILI; or    (b) a sequence of (a) with one or more amino acid additions, deletions or substitutions.    
     
     
         6 . The peptide of  claim 1 , wherein the peptide is a subsequence of a human VEGFR-2 comprising the sequence X-L/M-(X) 5 or 6 -L/T/F/G, where X is any amino acid.  
     
     
         7 . The peptide of  claim 6 , wherein the peptide comprises: 
 (a) the sequence VLLWEIFSL, ALIEGKNKT, AMFFWLLLV, VLLAVALWL, LMTKKNSTFV, FLSTLTIDGV, or WLLLVIILRT; or    (b) a sequence of (a) with one or more amino acid additions, deletions or substitutions.    
     
     
         8 . The peptide of  claim 6 , wherein the peptide binds to an HLA-A2 molecule.  
     
     
         9 . An isolated antigen presenting cell (APC) that presents the isolated peptide of  claim 1  on a cell surface MHC Class I molecule.  
     
     
         10 . The APC of  claim 9 , comprising a dendritic cell.  
     
     
         11 . The APC of  claim 10 , comprising a human dendritic cell.  
     
     
         12 . The APC of  claim 9 , wherein the APC is contacted with the peptide comprising a subsequence of a Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2).  
     
     
         13 . A pharmaceutical composition comprising: 
 (a) at least one isolated or synthetic peptide that binds to a Major Histocompatibility (MHC) Class I molecule comprising a subsequence of a Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2); or    b) an isolated antigen presenting cell (APC) that presents the at least one peptide of (a) on a cell surface MHC Class I molecule; and    a pharmaceutically acceptable carrier.    
     
     
         14 . The pharmaceutical composition of  claim 13 , comprising a plurality of different peptides or an APC that presents a plurality of different peptides.  
     
     
         15 . The pharmaceutical composition of  claim 13 , wherein the pharmaceutical composition is an immunogenic composition.  
     
     
         16 . The pharmaceutical composition of  claim 13 , further comprising an adjuvant.  
     
     
         17 . A method of eliciting an immune response against a VEGFR-2 comprising: 
 administering to a subject an immunologically effective amount of the pharmaceutical composition of  claim 13 .    
     
     
         18 . The method of  claim 17 , wherein eliciting an immune response against VEGFR-2 inhibits angiogenesis  
     
     
         19 . The method of  claim 17 , comprising administering the pharmaceutical composition to a subject with a tumor.  
     
     
         20 . The method of  claim 19 , wherein the tumor is a solid tumor or metastasis thereof.  
     
     
         21 . The method of  claim 20 , wherein administration of the pharmaceutical composition elicits an immune response that prevents or reduced neovascularization by the tumor or a metastasis thereof.  
     
     
         22 . The method of  claim 17 , further comprising administering at least one chemotherapeutic agent to the subject.  
     
     
         23 . The method of  claim 17 , further comprising administering at least one cytokine or immunostimulatory agent to the subject.  
     
     
         24 . The method of  claim 17 , wherein the pharmaceutical composition further comprises an adjuvant.  
     
     
         25 . The method of  claim 17 , comprising an autologous APC.  
     
     
         26 . The method of  claim 17 , wherein the subject is a human.  
     
     
         27 . A method of ameliorating an autoimmune disease, comprising: 
 administering to a subject a therapeutically effective amount of the pharmaceutical composition of  claim 13 .    
     
     
         28 . The method of  claim 27 , wherein the autoimmune disease is rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, diabetes and/or an inflammatory skin disorder.  
     
     
         29 . The method of  claim 27 , wherein the pharmaceutical composition further comprises an adjuvant.  
     
     
         30 . The method of  claim 27 , comprising an autologous APC.  
     
     
         31 . The method of  claim 27 , wherein the subject is a human.