Diefenbach Catherine S M, Gnjatic Sacha, Sabbatini Paul, Aghajanian Carol, Hensley Martee L, Spriggs David R, Iasonos Alexia, Lee Helen, Dupont Bo, Pezzulli Sandra, Jungbluth Achim A, Old Lloyd J, Dupont Jakob
Department of Medicine, Memorial Sloan-Kettering Cancer Center,New York, New York 10021, USA.
Clin Cancer Res. 2008 May 1;14(9):2740-8. doi: 10.1158/1078-0432.CCR-07-4619.
The cancer-testis antigen NY-ESO-1 is expressed by >40% of advanced epithelial ovarian cancers and is a promising immunotherapeutic target. In this study, we describe the effects of vaccination with the HLA-A*0201-restricted NY-ESO-1b peptide on patients with epithelial ovarian cancer in high-risk first remission.
After primary surgery and chemotherapy, high-risk epithelial ovarian cancer patients in first clinical remission received NY-ESO-1b peptide and Montanide every 3 weeks for five vaccinations. Tumor expression was evaluated by immunohistochemistry. Toxicity was monitored using National Cancer Institute Common Toxicity Criteria Scale Version 2. NY-ESO-1 specific humoral immunity (ELISA), T-cell immunity (tetramer and ELISPOT), and delayed-type hypersensitivity were assessed on weeks 0, 1, 4, 7, 10, 13, and 16.
Treatment-related adverse events included grade 1 fatigue, anemia, pruritus, myalgias, and hyperthyroidism and grade 2 hypothyroidism. There were no grade 3/grade 4 adverse events. Three of four patients (75%) with NY-ESO-1-positive tumor showed T-cell immunity by tetramer (0.6-9.5%) and ELISPOT (range, 35-260 spots). Four of five patients (80%) with NY-ESO-1-negative tumor showed T-cell immunity by tetramer (1.0-12.1%) and/or ELISPOT (range, 35-400 spots). With a median follow-up of 11.3 months, six of nine patients (67%) have recurred, with a median progression-free survival of 13 months (95% confidence interval, 11.2 months-not reached). Three of nine patients remain in complete clinical remission at 25, 38, and 52 months.
Vaccination of high-risk HLA-A*0201-positive epithelial ovarian cancer patients with NY-ESO-1b and Montanide has minimal toxicity and induces specific T-cell immunity in patients with both NY-ESO-1-positive and NY-ESO-1-negative tumors. Additional study is warranted.
癌症睾丸抗原NY-ESO-1在超过40%的晚期上皮性卵巢癌中表达，是一个很有前景的免疫治疗靶点。在本研究中，我们描述了用HLA-A*0201限制性NY-ESO-1b肽进行疫苗接种对处于高危首次缓解期的上皮性卵巢癌患者的影响。
在初次手术和化疗后，处于首次临床缓解期的高危上皮性卵巢癌患者每3周接受一次NY-ESO-1b肽和Montanide疫苗接种，共接种5次。通过免疫组织化学评估肿瘤表达情况。使用美国国立癌症研究所通用毒性标准第2版监测毒性。在第0、1、4、7、10、13和16周评估NY-ESO-1特异性体液免疫（ELISA）、T细胞免疫（四聚体和ELISPOT）以及迟发型超敏反应。
与治疗相关的不良事件包括1级疲劳、贫血、瘙痒、肌痛和甲状腺功能亢进以及2级甲状腺功能减退。没有3/4级不良事件。4例NY-ESO-1阳性肿瘤患者中有3例（75%）通过四聚体检测（0.6 - 9.5%）和ELISPOT检测（范围为35 - 260个斑点）显示出T细胞免疫。5例NY-ESO-1阴性肿瘤患者中有4例（80%）通过四聚体检测（1.0 - 12.1%）和/或ELISPOT检测（范围为35 - 400个斑点）显示出T细胞免疫。中位随访11.3个月，9例患者中有6例（67%）复发，中位无进展生存期为13个月（95%置信区间，11.2个月 - 未达到）。9例患者中有3例在25、38和52个月时仍处于完全临床缓解状态。
用NY-ESO-1b和Montanide对高危HLA-A*0201阳性上皮性卵巢癌患者进行疫苗接种毒性极小，并能在NY-ESO-1阳性和NY-ESO-1阴性肿瘤患者中诱导特异性T细胞免疫。有必要进行进一步研究。
