| Abstract: |
Cancer-testis (CT) antigens are ideal vaccine targets since their expression is restricted in adult tissues to testicular germ cells and a subset of cancers. The frequency of expression in transitional cell carcinomas (TCCs) of NY-ESO-1, the most immunogenic CT antigen to date, and its closely related gene LAGE-1 was studied. NY-ESO-1 and LAGE-1 antigen expression were found to occur frequently in high-grade TCC tumors. On an MSKCC IRB-approved protocol, 68 patient specimens were collected prospectively at the time of transurethral resection or cystectomy, of which 43 were read pathologically as high-grade tumors (pCIS, pTaG3, pT1, pT2, pT3, and pT4), 8 as low-grade tumors (pTaG1, pTaG2), and 17 as disease-free samples. These 68 samples were analyzed by immunohistochemistry (IHC) and/or RT-PCR. There were also an additional 53 paraffin-embedded specimens studied retrospectively by IHC, of which 39 were high-grade tumors and 14 were low-grade tumors. Cumulatively, our data indicate that NY-ESO-1 and/or LAGE-1 are expressed in 39/82 (48%) high-grade TCC and 3/22 (14%) low-grade TCC samples when analyzed by RT-PCR and/or IHC. Immunological assessment of these patients' sera identified one patient, whose tumor homogeneously expressed NY-ESO-1, which had detectable antibodies against NY-ESO-1 and LAGE-1. Further analysis of this patient, who remains clinically without evidence of disease 24 months after cystectomy for high-grade pT4 disease, revealed T-cell immunity against NY-ESO-1. This patient's T-cell response was determined to be specific for a new NY-ESO-1 epitope, p94-102, in the context of HLA-B35. |
| Keywords: |
immunohistochemistry; survival; adult; aged; aged, 80 and over; middle aged; survival analysis; genetics; cd8+ t lymphocyte; cd8-positive t-lymphocytes; proteins; metabolism; reverse transcription polymerase chain reaction; protein; membrane proteins; pathology; tumor antigen; bladder tumor; urinary bladder neoplasms; gene expression regulation; gene expression regulation, neoplastic; membrane antigen; immunology; antigens, neoplasm; messenger rna; reverse transcriptase polymerase chain reaction; rna, messenger; epitope; ctag1b protein, human; membrane protein; carcinoma, transitional cell; epitopes, t-lymphocyte; transitional cell carcinoma; antigens, surface; humans; human; male; female; article; ctag2 protein, human
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