Cancer Immunity 3:19 (2003)

Frequency of NY-ESO-1 and LAGE-1 expression in bladder cancer and evidence of a new NY-ESO-1 T-cell epitope in a patient with bladder cancer

Padmanee Sharma^1,2, Sacha Gnjatic¹, Achim A. Jungbluth¹, Barbara Williamson¹, Harry Herr³, Elisabeth Stockert^1*, Guido Dalbagni³, S. Machele Donat³, Victor E. Reuter⁴, Darren Santiago¹, Yao-Tseng Chen⁵, Dean F. Bajorin², Gerd Ritter¹, and Lloyd J. Old¹

¹Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, USA
²Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
³Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
⁴Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
⁵Department of Pathology, Weill Medical College of Cornell University, New York, NY, USA
^*Deceased September 21, 2002

Keywords: human, bladder cancer, NY-ESO-1, LAGE-1, immunohistochemistry, RT-PCR, T lymphocyte epitopes

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.