Cellular and Humoral Immune Responses Induced by an HLA Class I-restricted Peptide Cancer Vaccine Targeting WT1 Are Associated With Favorable Clinical Outcomes in Advanced Ovarian Cancer.
Cellular and Humoral Immune Responses Induced by an HLA Class I-restricted Peptide Cancer Vaccine Targeting WT1 Are Associated With Favorable Clinical Outcomes in Advanced Ovarian Cancer.
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DOI：
10.1097/cji.0000000000000405
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发表时间：
2022-01-01
期刊：
影响因子：
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通讯作者：
Sugiyama H
中科院分区：
文献类型：
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作者：
Nishida S;Morimoto S;Oji Y;Morita S;Shirakata T;Enomoto T;Tsuboi A;Ueda Y;Yoshino K;Shouq A;Kanegae M;Ohno S;Fujiki F;Nakajima H;Nakae Y;Nakata J;Hosen N;Kumanogoh A;Oka Y;Kimura T;Sugiyama H
补充数字内容可在文本中找到。靶向Wilms ' tumor 1 （WT1）的HLA-A*24:02 -限制性肽疫苗（WT1疫苗）是一种有前景的卵巢癌治疗策略。然而，其疗效因患者而异。在这项研究中，我们分析了标准化疗难治性晚期或复发卵巢癌患者的wt1特异性免疫反应及其与临床结果的关系。在25例患者中，连续3个月每周皮下注射WT1疫苗，此后每两周注射一次，直到疾病进展或出现严重不良事件。我们检测了Wilms肿瘤1特异性细胞毒性T淋巴细胞（wt1 - ctl）和Wilms肿瘤1肽特异性免疫球蛋白G （WT1235-IgG）。接种疫苗后，CD8+ T淋巴细胞中WT1-CTL四聚体高亲和人群百分比（%tet-hi WT1-CTL）和WT1235-IgG滴度均显著升高，但均极低或低于接种前的检测限（%tet-hi WT1-CTL: 0.003% ~ 0.103%; WT1235-IgG: <0.05 ~ 0.077 U/mL）。% et-hi WT1-CTL≥0.25% （n=6）或WT1235-IgG≥0.10 U/mL （n=12）的患者的无进展生存期明显长于其他组。此外，WT1235-IgG的升高与更长的无进展生存期相对应（P=0.0496）。在全身性炎症患者中，正如c反应蛋白水平升高所证明的那样，tet-hi WT1-CTL或WT1235-IgG的诱导不足。血清白蛋白水平降低、多发肿瘤病变、工作状态不佳和腹水过多对WT1疫苗的临床效果产生负面影响。总之，WT1疫苗可诱导难治性卵巢癌患者的抗原特异性细胞免疫和体液免疫。%t -hi WT1- ctl和WT1235-IgG水平都是WT1疫苗的预后标志物。
Supplemental Digital Content is available in the text. The HLA-A*24:02–restricted peptide vaccine targeting Wilms’ tumor 1 (WT1) (WT1 vaccine) is a promising therapeutic strategy for ovarian cancer; however, its efficacy varies among patients. In this study, we analyzed WT1-specific immune responses in patients with advanced or recurrent ovarian cancer that was refractory to standard chemotherapies and their associations with clinical outcomes. In 25 patients, the WT1 vaccine was administered subcutaneously weekly for 3 months and biweekly thereafter until disease progression or severe adverse events. We assessed Wilms’ tumor 1–specific cytotoxic T lymphocytes (WT1-CTLs) and Wilms’ tumor 1 peptide-specific immunoglobulin G (WT1235-IgG). After vaccination, the percentage of tetramer high-avidity population of WT1-CTLs among CD8+ T lymphocytes (%tet-hi WT1-CTL) and the WT1235-IgG titer increased significantly, although the values were extremely low or below the limit of detection before vaccination (%tet-hi WT1-CTL: 0.003%–0.103%.; WT1235-IgG: <0.05–0.077 U/mL). Patients who had %tet-hi WT1-CTL of ≥0.25% (n=6) or WT1235-IgG of ≥0.10 U/mL (n=12) had a significantly longer progression-free survival than those of patients in the other groups. In addition, an increase in WT1235-IgG corresponded to a significantly longer progression-free survival (P=0.0496). In patients with systemic inflammation, as evidenced by elevated C-reactive protein levels, the induction of tet-hi WT1-CTL or WT1235-IgG was insufficient. Decreased serum albumin levels, multiple tumor lesions, poor performance status, and excess ascites negatively influenced the clinical effectiveness of the WT1 vaccine. In conclusion, the WT1 vaccine induced antigen-specific cellular and humoral immunity in patients with refractory ovarian cancer. Both %tet-hi WT1-CTL and WT1235-IgG levels are prognostic markers for the WT1 vaccine.