Expression of potential target antigens for immunotherapy on primary and metastatic prostate cancers.
Defining the expression of tumor-associated antigens on primary and metastatic prostate cancer is the crucial first step in selecting appropriate targets for immune attack. In this study, the distribution of the tumor-associated antigens GM2, Tn, sTn, Thompson-Friedenreich antigen (TF), Globo H, Le(y), MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC7, carcinoembryonic antigen, beta chain of human chorionic gonadotropin (hCG beta), HER2/neu, PSMA, and KSA on primary and metastatic prostate cancer and 16 types of normal tissues was compared by immunohistochemistry, using a panel of well-characterized monoclonal antibodies. Our results show that GM2, KSA, and MUC2 were strongly expressed on 8 or 9 of 9 metastatic prostate cancer biopsy specimens and, with PSMA, hCG beta, TF, Tn, and sTn, on 8 or more of 11 primary prostate cancer specimens. Tn, MUC1, and PSMA were expressed on 4-6 of 9 metastatic specimens. The remaining antigens were expressed on no more than three of nine metastatic specimens. Normal tissues were also tested with all antibodies. With regard to the eight antigens most widely expressed on prostate cancers, PSMA was not expressed significantly on any of the normal tissues except prostate epithelium. Tn, sTn, hCG beta, and MUC2 were detected on up to 3 of 10 types of normal epithelia. GM2, TF, MUC1, and KSA were more broadly distributed on normal epithelia, all primarily at the secretory borders. STn, KSA, and hCG beta were also detected in the testis, and GM2 was expressed on gray matter of brain. From the 30 antigens that we have screened, this study provides the basis for selecting GM2, TF, Tn, sTn, hCG beta, MUC1, MUC2, KSA, and PSMA as target antigens for specific immunotherapy of prostate cancer.
Zhang
S
S
Clinical Immunology Service, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Zhang
H S
HS
Reuter
V E
VE
Slovin
S F
SF
Scher
H I
HI
Livingston
P O
PO
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000276:immunology; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002240:Carbohydrate Sequence; D000939:Epitopes; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D019496:Cancer Vaccines; D000939:Epitopes