Sharma Padmanee, Gnjatic Sacha, Jungbluth Achim A, Williamson Barbara, Herr Harry, Stockert Elisabeth, Dalbagni Guido, Donat S Machele, Reuter Victor E, Santiago Darren, Chen Yao-Tseng, Bajorin Dean F, Old Lloyd J
Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Cancer Immun. 2003 Dec 18;3:19.
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.
癌-睾丸（CT）抗原是理想的疫苗靶点，因为它们在成人组织中的表达仅限于睾丸生殖细胞和一部分癌症。研究了迄今为止免疫原性最强的CT抗原NY-ESO-1及其密切相关基因LAGE-1在移行细胞癌（TCC）中的表达频率。发现NY-ESO-1和LAGE-1抗原表达在高级别TCC肿瘤中频繁出现。根据MSKCC机构审查委员会批准的方案，在经尿道切除术或膀胱切除术时前瞻性收集了68份患者标本，其中43份经病理诊断为高级别肿瘤（pCIS、pTaG3、pT1、pT2、pT3和pT4），8份为低级别肿瘤（pTaG1、pTaG2），17份为无疾病样本。对这68份样本进行了免疫组织化学（IHC）和/或逆转录-聚合酶链反应（RT-PCR）分析。另外还有53份石蜡包埋标本通过IHC进行回顾性研究，其中39份为高级别肿瘤，14份为低级别肿瘤。总体而言，我们的数据表明，通过RT-PCR和/或IHC分析，NY-ESO-1和/或LAGE-1在39/82（48%）的高级别TCC样本和3/22（14%）的低级别TCC样本中表达。对这些患者血清的免疫学评估发现1例患者，其肿瘤均匀表达NY-ESO-1，该患者血清中可检测到针对NY-ESO-1和LAGE-1的抗体。对该患者进行进一步分析，其因高级别pT4疾病接受膀胱切除术后24个月临床仍无疾病证据，结果显示其存在针对NY-ESO-1的T细胞免疫。确定该患者的T细胞反应在HLA-B35背景下对一个新的NY-ESO-1表位p94-102具有特异性。
