Compositions for and methods of treating and preventing cancer targeting tumor associated carbohydrate antigens

Abstract

Compositions useful to induce anti-TACA immune response and kits comprising the same and methods of using the compositions to treat and prevent cancer are disclosed. Isolated human antibodies which bind to a carbohydrate mimetic peptide and methods of making the same and using the same to treat and prevent cancer are disclosed. Isolated human NK cells useful to kill tumor cells, and isolated human dendritic cells, and methods of making the same and using the same to treat and prevent cancer are disclosed.

1 . A method of treating a human who has been diagnosed as having cancer that is selected from the group consisting of: ER+/PR+/Her2-breast cancer; lung cancer; melanoma; pancreatic cancer; brain cancer; and ovarian cancer; the method comprising administering to said human a composition comprising SEQ ID NO:1 linked to a CD4+ helper T cell epitope. 
     
     
         2 . The method of  claim 1  wherein the CD4 +  helper T cell epitope is a PADRE peptide selected from the group consisting of: SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5 and dAla-Lys -CHAla-Val-Ala-Ala-Trp-Thr-Leu-Lys-Ala-Ala-dAla in which dAla refers to a D amino acid Alanine and CHAla refers to cyclohexylalanine. 
     
     
         3 . The method of  claim 1  wherein the SEQ NO:1 linked to the CD4 +  helper T cell epitope comprises Trp-Arg-Tyr-Thr-Ala-Pro-Val-His-Leu-Gly-Asp-Gly-dAla-Lys-CHAla-Val-Ala -Ala-Trp-Thr-Leu-Lys-Ala-Ala-dAla in which dAla at positions 13 and 25 refers to a D amino acid Alanine and CHAla at position 15 refers to cyclohexylalanine. 
     
     
         4 . The method of  claim 1  wherein the SEQ ID NO:1 linked to the CD4 +  helper cell epitope is a compound having the structure of Formula 1: 
       
         
           
                 
               
                   Formula 1 
                 
                   Trp-Arg-Tyr-Thr-Ala-Pro-Val-His-Leu-Gly-Asp-Gly- 
                 
                     
                 
                   dAla-Lys-CHAla-Val-Ala-Ala-Trp-Thr-Leu-Lys-Ala- 
                 
                     
                 
                   Ala-dAla-NH 2   
                 
             
                
                
                
                
                
                
               
            
           
         
       
       wherein Ala13 and Ala25 are each D amino acids shown as dALa and Ala at position 15 is cyclohexylalanine, a modified L configuration Alanine shown as CHAla. 
     
     
         5 . The method of  claim 4  wherein the composition further comprises an adjuvant. 
     
     
         6 . The method of  claim 5  wherein the adjuvant is selected from the group consisting of an oil and surfactant adjuvant and QS21 adjuvant. 
     
     
         7 . The method of  claim 5  wherein adjuvant is an oil and surfactant adjuvant, wherein the oil is mineral oil and the surfactant is mannide monooleate. 
     
     
         8 . The method of  claim 7  wherein the human has been diagnosed as having lung cancer. 
     
     
         9 . The method of  claim 4  wherein the human has been diagnosed as having lung cancer. 
     
     
         10 . The method of  claim 4  wherein the composition comprises the compound having the structure of Formula I in an amount selected from the group consisting of: at least 300 μg, at least 500 μg, and at least 1000 μg. 
     
     
         11 . The method of  claim 4  further comprising treating the human with one or more anti-cancer chemotherapeutics, anti-cancer radioactive agent and/or with anti-cancer radiation therapy. 
     
     
         12 . The method of  claim 4  further comprising treating the human with one or more anti-cancer chemotherapeutics selected from the group consisting of: doxorubicin, cyclophosphamide, docetaxel, cisplatin, vinorelbine, bortezomib, adriamycin, trastuzumab, paclitaxel, tamoxifen and pertuzumab. 
     
     
         13 . The method of  claim 4  wherein the human is further treated with surgery. 
     
     
         14 . The method of  claim 1  Wherein the composition further comprises an adjuvant. 
     
     
         15 . The method of  claim 14  wherein the adjuvant is selected from the group consisting of an oil and surfactant adjuvant and QS21 adjuvant. 
     
     
         16 . The method of  claim 14  wherein adjuvant is an oil and surfactant adjuvant, wherein the oil is mineral oil and the surfactant is mannide monooleate. 
     
     
         17 . The method of  claim 1  herein the human has been diagnosed as having lung cancer. 
     
     
         18 . The method of  claim 1  further comprising treating the human with one or more anti-cancer chemotherapeutics, anti-cancer radioactive agent and/or with anti-cancer radiation therapy. 
     
     
         19 . The method of  claim 1  further comprising treating the human with one or more anti-cancer chemotherapeutics selected from the group consisting of: doxorubicin, cyclophosphamide, docetaxel, cisplatin, vinorelbine, bortezomib, adriamycin, trastuzumab, paclitaxel, tamoxifen and pertuzumab. 
     
     
         20 . The method of  claim 1  wherein the human is further treated with surgery.