Prostate cancer and melanoma antigens

Abstract

Methods for identifying a human subject as a candidate for further prostate cancer or melanoma examination are disclosed. Also disclosed are methods for determining whether an immune therapy has elicited a tumor-specific immune response in a prostate cancer or melanoma patient. Further disclosed are kits that can be used to practice the above methods. Methods for identifying candidate compounds for further testing as preventive or therapeutic agents for melanoma are also disclosed.

1 . A method for identifying a human subject as a candidate for further prostate cancer examination comprising the step of:
 determining whether the human subject has developed an immune reaction to a prostate cancer antigen selected from SSX-2 encoded by SEQ ID NO: 60 or a conservatively modified variant thereof, MAD-Pro-30 (SEQ ID NO: 58), MAD-Pro-42 (SEQ ID NO: 61), transgelin encoded by SEQ ID NO: 62 or a conservatively modified variant thereof, ZCWCC3 (SEQ ID NO: 63), ACAA1 (SEQ ID NO: 64), actinin (SEQ ID NO: 65), and NFX2 (SEQ ID NO: 66) wherein the presence of an immune reaction indicates that the human subject is a candidate for further prostate cancer examination.   
     
     
         2 . The method of  claim 1 , wherein the antigen is selected from SSX-2 encoded by a nucleic acid comprising SEQ ID NO: 60 or a conservatively modified variant thereof, MAD-Pro-30 (SEQ ID NO: 58), MAD-Pro-42 (SEQ ID NO: 61), transgelin (SEQ ID NO: 62), ZCWCC3 (SEQ ID NO: 63), and ACAA1 (SEQ ID NO: 64). 
     
     
         3 . The method of  claim 1 , wherein the antigen is MAD-Pro-30 (SEQ ID NO: 58). 
     
     
         4 . The method of  claim 3 , wherein whether the human subject developed an immune reaction to antigens in an antigen panel is determined, and wherein the panel comprises MAD-Pro-30 (SEQ ID NO: 58), SSX-2 encoded by a nucleic acid comprising the nucleotide sequence of SEQ ID NO: 60 or a conservatively modified variant thereof, androgen receptor (AR) ligand binding domain (SEQ ID NO: 59), and MAD-Pro-22 (PSA) (SEQ ID NO: 57). 
     
     
         5 . The method of  claim 1 , wherein the development of an immune reaction is determined by testing whether a blood sample from the human subject contains an antibody to an antigen. 
     
     
         6 . A method for determining whether an immune therapy has elicited a tumor-specific immune response in a prostate cancer patient, the method comprising the steps of:
 providing an immune therapy to a prostate cancer patient; and   determining whether the patient developed an immune reaction to a prostate cancer antigen selected from SSX-2 encoded by SEQ ID NO: 60 or a conservatively modified variant thereof, MAD-Pro-30 (SEQ ID NO: 58), MAD-Pro-42 (SEQ ID NO: 61), transgelin encoded by the nucleotide sequence of SEQ ID NO: 62 or a conservatively modified variant thereof, ZCWCC3(SEQ ID NO: 63), ACAA1 (SEQ ID NO: 64), actinin (SEQ ID NO: 65), and NFX2 (SEQ NO: 66), wherein the presence of an immune reaction indicates that the therapy has elicited a tumor-specific immune response.   
     
     
         7 . The method of  claim 6 , wherein the antigen is selected from SSX-2 encoded by SEQ ID NO: 60 or a conservatively modified variant thereof, MAD-Pro-30 (SEQ ID NO: 58), MAD-Pro-42 (SEQ ID NO: 61), transgelin encoded by SEQ ID NO: 62 or a conservatively modified variant thereof, ZCWCC3 (SEQ ID NO: 63), and ACAA1 (SEQ ID NO: 64). 
     
     
         8 . The method of  claim 6 , wherein the antigen is MAD-Pro-30 (SEQ ID NO: 58). 
     
     
         9 . The method of  claim 8 , wherein whether the prostate cancer patient developed an immune reaction to antigens in an antigen panel is determined, and wherein the panel comprises MAD-Pro-30 (SEQ ID NO: 58), SSX-2 encoded by SEQ ID NO: 60 or a conservatively modified variant thereof, androgen receptor (AR) ligand binding domain (SEQ ID NO: 59), and MAD-Pro-22 (PSA) (SEQ ID NO: 57). 
     
     
         10 . The method of  claim 6 , wherein the immune therapy is a non-antigen-specific immune therapy. 
     
     
         11 . The method of  claim 6 , wherein the development of an immune reaction is determined by testing whether a blood sample from the prostate cancer patient contains an antibody to an antigen. 
     
     
         12 . (canceled) 
     
     
         13 . A method for identifying a human subject as a candidate for further melanoma examination comprising the step of:
 determining whether the human subject has developed an immune reaction to a melanoma antigen selected from MAD-CT-2 encoded by SEQ ID NO: 67 or a conservatively modified variant thereof, MAD-CT-1 (SEQ ID NO: 68), and PAGE-1 (SEQ ID NO: 69), wherein the presence of an immune reaction indicates that the human subject is a candidate for further melanoma examination.   
     
     
         14 . The method of  claim 13 , wherein the antigen is MAD-CT-2. 
     
     
         15 . The method of  claim 14 , wherein whether the human subject developed an immune reaction to antigens in an antigen panel is determined, and wherein the panel comprises MAD-CT-1 (SEQ ID NO: 68), PAGE-1 (SEQ ID NO: 69), SSX-2 encoded by SEQ ID NO: 60 or a conservatively modified variant thereof, and NY-ESO-1 (SEQ ID NO: 70). 
     
     
         16 . The method of  claim 13 , wherein the development of an immune reaction is determined by testing whether a blood sample from the human subject contains an antibody to an antigen. 
     
     
         17 . A method for determining whether an immune therapy has elicited a tumor-specific immune response in a melanoma patient, the method comprising the steps of:
 providing an immune therapy to a melanoma patient; and   determining whether the patient developed an immune reaction to a melanoma antigen selected from MAD-CT-2 encoded by SEQ ID NO: 67 or a conservatively modified variant thereof, MAD-CT-1 (SEQ ID NO: 68), and PAGE-1 (SEQ ID NO: 69), wherein the presence of an immune reaction indicates that the therapy has elicited a tumor-specific immune response.   
     
     
         18 . The method of  claim 17 , wherein the antigen is MAD-CT-2 encoded by SEQ ID NO: 67 or a conservatively modified variant thereof. 
     
     
         19 . The method of  claim 18 , wherein whether the melanoma patient developed an immune reaction to antigens in an antigen panel is determined, and wherein the panel comprises MAD-CT-1 (SEQ ID NO: 68), PAGE-1 (SEQ ID NO: 69), SSX-2 encoded by SEQ ID NO: 60 or a conservatively modified variant thereof, and NY-ESO-1 (SEQ ID NO: 70). 
     
     
         20 . The method of  claim 17 , wherein the immune therapy is a non-antigen-specific immune therapy. 
     
     
         21 . The method of  claim 17 , wherein the development of an immune reaction is determined by testing whether a blood sample from the melanoma patient contains an antibody to an antigen. 
     
     
         22 . A method for identifying a human subject as a candidate for further melanoma examination comprising the step of:
 determining whether the cells in a region of the subject's skin suspected of being malignant express MAD-CT-2 encoded by SEQ ID NO: 67 or a conservatively modified variant thereof, wherein the expression of MAD-CT-2 indicates that the subject is a candidate for further melanoma examination.   
     
     
         23 . A method for identifying candidate compounds for further testing as preventive or therapeutic agents for melanoma, the method comprising the steps of:
 providing cells that express MAD-CT-2 encoded by SEQ ID NO: 67 or a conservatively modified variant thereof;   exposing the cells to a test compound;   determining the expression of level of MAD-CT-2 in the exposed cells; and   comparing the expression level in the exposed cells to that of corresponding control cells that are not exposed to the test compound, wherein a lower expression level than that in the control cells indicates that the compound is a candidate for further testing as a preventive or therapeutic agent for melanoma.   
     
     
         24 . A kit comprising:
 a first polypeptide that comprises MAD-CT-2 encoded by SEQ ID NO: 67 or a conservatively modified variant thereof;   a second polypeptide that comprises SSX-2 encoded by SEQ ID NO: 60 or a conservatively modified variant thereof; and   a third polypeptide that comprises NY-ESO-1 (SEQ ID NO: 70).