Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination
Analysis of peripheral and local anti-tumor immune response in esophageal cancer patients after NY-ESO-1 protein vaccination
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DOI：
10.1002/ijc.23810
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发表时间：
2008-11-15
影响因子：
6.4
通讯作者：
Nakayama, Eiichi
中科院分区：
文献类型：
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作者：
Wada, Hisashi;Sato, Eiichi;Nakayama, Eiichi
NY-ESO-1 抗原是一类癌症/睾丸抗原的原型。我们对 13 名晚期癌症患者进行了使用 NY-ESO-1 全蛋白作为癌症疫苗的临床试验。我们最近报道，疫苗在 9 名癌症患者（包括 4 名食道癌患者）中引发了体液和细胞免疫反应，并且在 5 名可评估患者中的 4 名中也观察到了临床反应。在这项研究中，我们分析了 8 名食管癌患者的反应，其中包括 4 名新入组患者。每两周给患者皮下注射由含胆固醇疏水化普鲁兰多糖配制而成的 NY-ESO-1 重组蛋白。在 8 名患者中，分别有 7 名、7 名和 6 名患者观察到抗体以及 CD4 和 CD8 T 细胞反应的诱导。在 6 名可评估患者中观察到 1 例 PR、2 例 SD 和 2 例混合临床反应。没有观察到明显的不良事件。此外，我们通过免疫组织化学分析了 4 名患者接种疫苗前后获得的肿瘤样本中的 NY-ESO-1 和 MHC I 类表达以及免疫细胞的浸润情况。结果显示，2名患者在接种疫苗后进展性肿瘤中CD4和CD8 T细胞浸润消失，1名患者CD68(+)巨噬细胞数量增加，1名患者肿瘤抗原丢失。通过接种 NY-ESO-1 疫苗，在食道癌患者中观察到 NY-ESO-1 免疫力的诱导和一些更好的临床结果。然而。接种疫苗后，肿瘤最终通过各种机制生长。 (C) 2008 Wiley-Liss, Inc.
NY-ESO-1 antigen is a prototype of a class of cancer/testis antigens. We carried out a clinical trial using NY-ESO-1 whole protein as a cancer vaccine for 13 advanced cancer patients. We have recently reported that vaccine elicited humoral and cellular immune responses in 9 cancer patients including 4 esophageal cancer patients, and clinical responses were also observed in 4 of 5 evaluable patients. In this study, we analyzed the responses in 8 esophageal cancer patients including 4 newly enrolled patients. Patients were injected subcutaneously at biweekly intervals with NY-ESO-1 recombinant protein formulated with cholesterol-bearing hydrophobized pullulan. Induction of antibody, and CD4 and CD8 T-cell responses were observed in 7, 7 and 6 patients, respectively, out of 8 patients. 1 PR, 2 SD and 2 mixed clinical responses were observed in 6 evaluable patients. No significant adverse events were observed. Furthermore, we analyzed NY-ESO-1 and MHC class I expression and the infiltration of immune cells into tumor samples obtained before and after vaccination from 4 patients by immunohistochemistry. The results showed 2 patients with disappearance of CD4 and CD8 T-cell infiltration, I patient with increase in the number of CD68(+) macrophages and 1 patient with tumor antigen loss in the progressive tumors following vaccinations. The induction of NY-ESO-1 immunity and some preferable clinical outcomes were observed in esophageal cancer patients by vaccination with NY-ESO-1. However. the tumors grew eventually by various mechanisms after vaccination. (C) 2008 Wiley-Liss, Inc.