Biomarkers for prostate cancer and methods for their detection

Abstract

The invention provides a method for predicting the clinical response to a cancer vaccine in a patient having cancer, a method for determining the immune response to a cancer vaccine in a patient having cancer who has been administered a cancer vaccine, a method for determining the long-term survival in a patient having cancer, corresponding kits therefor, as well as methods of for improving the efficacy of a virus-based vaccine.

1 .- 42 . (canceled) 
     
     
         43 . A method for predicting the clinical response to a poxvirus-based vaccine in a patient and treating cancer in the patient, the method comprising:
 obtaining a serum sample from a patient having cancer who has not been previously administered the poxvirus-based vaccine;   assaying the serum sample to determine the levels of antibodies in the patient to at least one glycan and/or glycoprotein antigen selected from the group consisting of Sialylα2-6Galβ1-4Glc-(6′SLac), Sialylα2-3Galβ1-4(Fucα1-3)GlcNAc-(SLeX), Sialylα2-3Galβ1-4Glc-(GM3), Fucα1-2Galβ1-3GlcNAcβ1-3Galβ1-4Glcβ-(BG-H1), GalNAcβ1-4Galβ-(GA2 di ), Galβ1-4GlcNAcβ1-6(Galβ1-4GlcNAcβ1-3)Galβ-(LNnH), Galα1-3Gal-(B di ), Ac-Ser-(GalNAcα)Thr-Gly-Gly-(Ac-S-Tn(Thr)-G-G), BSM, Lactose, Galβ1-3GlcNAcβ1-3Galβ-(LNT), Fuc-b, Fuc-a, Galβ1-6Man-α-(Galb1-6Man-a), Galβ1-3GalNAcβ1-4Galβ1-(GA1), Galα1-4Galβ-(Gala1-4Galb), Manα1-6[Manα1-3]Manβ-(ManT), Galβ1-3GlcNAcβ1-3Galβ1-4GlcNAcβ1-3Galβ1-(pLNH), Rha-a-, GalNAcα1-3Galβ-(A di ), GalNAcα1-3(Fucα1-2)Galβ-(BG-A), Galβ1-3GalNAcβ1-4Galβ1-(GA1), fetuin, and Ac-Ser-(GalNAcα)Ser-Ser-Gly-(Ac-S-Tn(Ser)-S-G);   comparing the determined levels of antibodies to the at least one glycan and/or glycoprotein antigen to a control, so as to predict the clinical response to the poxvirus-based vaccine in the patient; and   treating the cancer by administering the poxvirus-based vaccine to the patient.   
     
     
         44 . The method of  claim 43 , wherein the serum sample is assayed to determine the levels of antibodies to at least two glycan and/or glycoprotein antigens selected from the group consisting of 6′SLac, SLeX, GM3, BG-H1, GA2 di , LNnH, B di , Ac-S-Tn(Thr)-G-G, BSM, Lactose, LNT, Fuc-b, Fuc-a, Galb1-6Man-a, GA1, Gala1-4Galb, ManT, pLNH, Rha-α, GalNAcα1-3Galβ-(A di ), GalNAcα1-3(Fucα1-2)Galβ- (BG-A), Galβ1-3GalNAcβ1-4Galβ1-(GA1), fetuin, and Ac-S-Tn(Ser)-S-G. 
     
     
         45 . The method of  claim 44 , wherein the serum sample is assayed to determine the levels of antibodies to at least three glycan and/or glycoprotein antigens selected from the group consisting of 6′SLac, SLeX, GM3, BG-H1, GA2 di , LNnH, B di , Ac-S-Tn(Thr)-G-G, BSM, Lactose, LNT, Fuc-b, Fuc-a, Galb1-6Man-a, GA1, Gala1-4Galb, ManT, pLNH, Rha-α, GalNAcα1-3Galβ-(A di ), GalNAcα1-3(Fucα1-2)Galβ-(BG-A), Galβ1-3GalNAcβ1-4Galβ1-(GA1), and Ac-S-Tn(Ser)-S-G. 
     
     
         46 . The method of  claim 45 , wherein the serum sample is assayed to determine the levels of antibodies to at least four glycan and/or glycoprotein antigens selected from the group consisting of 6′SLac, SLeX, GM3, BG-H1, GA2 di , LNnH, B di , Ac-S-Tn(Thr)-G-G, BSM, Lactose, LNT, Fuc-b, Fuc-a, Galb1-6Man-a, GA1, Gala1-4Galb, ManT, pLNH, Rha-α, GalNAcα1-3Galβ-(A di ), GalNAcα1-3(Fucα1-2)Galβ-(BG-A), Galβ1-3GalNAcβ1-4Galβ1-(GA1), fetuin, and Ac-S-Tn(Ser)-S-G. 
     
     
         47 . The method of  claim 46 , wherein the serum sample is assayed to determine the levels of antibodies to at least five glycan and/or glycoprotein antigens selected from the group consisting of 6′SLac, SLeX, GM3, BG-H1, GA2 di , LNnH, B di , Ac-S-Tn(Thr)-G-G, BSM, Lactose, LNT, Fuc-b, Fuc-a, Galb1-6Man-a, GA1, Gala1-4Galb, ManT, pLNH, Rha-α, GalNAcα1-3Galβ-(A di ), GalNAcα1-3(Fucα1-2)Galβ-(BG-A), Galβ1-3GalNAcβ1-4Galβ1-(GA1), fetuin, and Ac-S-Tn(Ser)-S-G. 
     
     
         48 . The method of  claim 43 , wherein the antibodies are selected from the group consisting of IgG, IgM, IgA, IgD, IgE, and combinations thereof. 
     
     
         49 . The method of  claim 43 , wherein the serum sample is assayed to determine the levels of IgM antibodies to BG-A. 
     
     
         50 . The method of  claim 43 , wherein the serum sample is assayed to determine one or more of the following: the levels of IgG antibodies to GA1, the levels of IgG antibodies to Rha-a, the levels of IgA antibodies to Fuc-a, the levels of Ig antibodies to LNnH, the levels of IgG antibodies to 6′SLac, and the levels of IgG antibodies to GM3. 
     
     
         51 . The method of  claim 43 , wherein levels of antibodies in the patient to GalNAcα1-3(Fucα1-2)Galβ-(BG-A) is determined. 
     
     
         52 . The method of  claim 43 , wherein the cancer is selected from the group consisting of prostate, breast, pancreatic, ovarian, gastric, head and neck, liver, lung, kidney, bone, brain, colorectal, uterine, skin, endometrial, esophageal, anal, oral, nasal, and rectal cancer. 
     
     
         53 . The method of  claim 43 , wherein the cancer is prostate cancer. 
     
     
         54 . The method of  claim 43 , wherein the poxvirus-based vaccine is selected from the group consisting of avipox-based vaccine, orthopox-based vaccine, cowpox-based vaccine, and camelpox-based vaccine. 
     
     
         55 . The method of  claim 43 , wherein the poxvirus-based vaccine is an avipox-based vaccine. 
     
     
         56 . The method of  claim 54 , wherein the avipox-based vaccine is a fowlpox-based vaccine. 
     
     
         57 . A method for determining the immune response to a poxvirus-based vaccine in a patient and treating cancer in the patient, the method comprising:
 obtaining a first serum sample from a patient having cancer who has not been previously administered the poxvirus-based vaccine;   treating the cancer in the patient by administering the poxvirus-based vaccine to the patient;   obtaining a second serum sample from the patient after administration of the poxvirus-based vaccine,   assaying the first and second serum samples to determine the first and second levels of antibodies, respectively, to at least one glycan and/or glycoprotein antigen selected from the group consisting of the Forssman antigen, GalNAcα1-3Galβ-(A di ), GalNAcα1-3(Fucα1-2)Galβ-(BG-A), the Tn antigen, the TF antigen, Sialylα2-3Galβ1-4(Fucα1-3)GlcNAc-(SLeX), Siaα2-3 Galβ1-3[Fucα1-4]GlcNAcβ1-(SLeA), Fucα1-2Galβ1-4(Fucα1-3)GlcNAc-(LeY), Sialylα2-6Galβ1-4Glc-(6′SLac), Sialylα2-3Galβ1-4Glc-(GM3), Fucα1-2Galβ1-3GlcNAcβ1-3Galβ1-4Glcβ-(BG-H1), GalNAcβ1-4Galβ-(GA2 di ), Galβ1-4GlcNAcβ1-6(Galβ1-4GlcNAcβ1-3)Galβ-(LNnH), Galα1-3Gal-(B di ), GalNAcα1-3(Fucα1-2)Galβ1-3(Fucα1-4)GlcNAcβ1-3 Galβ1-(A-LeB), and fetuin; and   comparing the determined first and second levels of antibodies to the at least one glycan and/or glycoprotein antigen, so as to determine the immune response to the poxvirus-based vaccine in the patient.   
     
     
         58 . The method of  claim 57 , wherein the first or second serum sample is assayed to determine the levels of antibodies to at least two glycan and/or glycoprotein antigens selected from the group consisting of Forssman antigen, 6′SLac, SLeX, GM3, BG-H1, GA2 di , LNnH, B di , Ac-S-Tn(Thr)-G-G, BSM, Lactose, LNT, Fuc-b, Fuc-a, Galb1-6Man-a, GA1, Gala1-4Galb, ManT, pLNH, Rha-α, GalNAcα1-3Galβ-(A di ), GalNAcα1-3(Fucα1-2)Galβ-(BG-A), Galβ1-3GalNAcβ1-4Galβ1-(GA1), fetuin, and Ac-S-Tn(Ser)-S-G. 
     
     
         59 . The method of  claim 58 , wherein the first or second serum sample is assayed to determine the levels of antibodies to at least three glycan and/or glycoprotein antigens selected from the group consisting of Forssman antigen, 6′SLac, SLeX, GM3, BG-H1, GA2 di , LNnH, B di , Ac-S-Tn(Thr)-G-G, BSM, Lactose, LNT, Fuc-b, Fuc-a, Galb1-6Man-a, GA1, Gala1-4Galb, ManT, pLNH, Rha-α, GalNAcα1-3Galβ-(A di ), GalNAcα1-3(Fucα1-2)Galβ-(BG-A), Galβ1-3GalNAcβ1-4Galβ1-(GA1), and Ac-S-Tn(Ser)-S-G. 
     
     
         60 . The method of  claim 59 , wherein the first or second serum sample is assayed to determine the levels of antibodies to at least four glycan and/or glycoprotein antigens selected from the group consisting of Forssman antigen, 6′SLac, SLeX, GM3, BG-H1, GA2 di , LNnH, B di , Ac-S-Tn(Thr)-G-G, BSM, Lactose, LNT, Fuc-b, Fuc-a, Galb1-6Man-a, GA1, Gala1-4Galb, ManT, pLNH, Rha-α, GalNAcα1-3Galβ-(A di ), GalNAcα1-3(Fucα1-2)Galβ-(BG-A), Galβ1-3GalNAcβ1-4Galβ1-(GA1), fetuin, and Ac-S-Tn(Ser)-S-G. 
     
     
         61 . The method of  claim 60 , wherein the first and second serum sample is assayed to determine the levels of antibodies to at least five glycan and/or glycoprotein antigens selected from the group consisting of Forssman antigen, 6′SLac, SLeX, GM3, BG-H1, GA2 di , LNnH, B di , Ac-S-Tn(Thr)-G-G, BSM, Lactose, LNT, Fuc-b, Fuc-a, Galb1-6Man-a, GA1, Gala1-4Galb, ManT, pLNH, Rha-α, GalNAcα1-3 Galβ-(A di ), GalNAcα1-3(Fucα1-2)Galβ-(BG-A), Galβ1-3GalNAcβ1-4Galβ1-(GA1), fetuin, and Ac-S-Tn(Ser)-S-G. 
     
     
         62 . The method of  claim 57 , wherein the antibodies are selected from the group consisting of IgG, IgM, IgA, IgD, IgE, and combinations thereof.