Efficacy of glypican-3-derived peptide vaccine therapy on the survival of patients with refractory ovarian clear cell carcinoma.
Efficacy of glypican-3-derived peptide vaccine therapy on the survival of patients with refractory ovarian clear cell carcinoma.
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DOI：
10.1080/2162402x.2016.1238542
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发表时间：
2016
期刊：
影响因子：
7.2
通讯作者：
Nakatsura T
中科院分区：
文献类型：
--
作者：
Suzuki S;Sakata J;Utsumi F;Sekiya R;Kajiyama H;Shibata K;Kikkawa F;Nakatsura T
与其他上皮性卵巢癌亚型相比，卵巢透明细胞癌（OCCC）已被公认为具有耐药性。因此，需要新的治疗方式与OCCC患者是化疗难治性。癌胚抗原磷脂酰肌醇蛋白聚糖-3（GPC-3）由大约一半的OCCC表达，是一个有前途的免疫靶点。本研究的目的是评估GPC 3肽疫苗对难治性OCCC患者的效果。我们在OCCC患者中进行了GPC 3衍生肽疫苗的II期试验。采用体外IFNγ ELISPOT法检测小鼠的免疫应答。我们还评估了对照组受试者，他们在同一时期接受了最好的支持治疗，没有接种疫苗。在2010年7月至2015年9月期间招募了32名患有难治性OCCC的患者，并接受了GPC 3肽疫苗接种。15名患者因一般状况进行性恶化而接种了不到6次疫苗，17名患者接种了至少6次疫苗。3例患者显示部分缓解为最佳总体缓解。GPC 3肽疫苗在24名采集了3次或更多次PBMC的患者中的15名中诱导了GPC 3特异性CTL应答。未接种GPC 3肽疫苗的姑息治疗患者的预后显著差于接种GPC 3肽疫苗的患者（癌症治疗后生存率：p = 0.002）。虽然疾病控制率不高，但我们的研究结果表明，GPC 3肽疫苗接种可能对延长难治性OCCC患者的生存期产生重大影响，使他们能够保持生活质量，而不会出现严重的毒性。
Compared with other epithelial ovarian carcinoma subtypes, ovarian clear cell carcinoma (OCCC) has been recognized to show chemoresistance. Therefore, new treatment modalities are required for patients with OCCC that is refractory to chemotherapy. The carcinoembryonic antigen glypican-3 (GPC3) is expressed by approximately half of OCCC and is a promising immunotherapeutic target. The purpose of this study was to evaluate the effect of GPC3 peptide vaccine against refractory OCCC patients. We conducted a phase II trial with a GPC3-derived peptide vaccine in OCCC patients. Immunological responses were analyzed by ex vivo IFNγ ELISPOT assay. We also evaluated control subjects, who received best supportive care without vaccinations during the same period. Thirty-two patients with refractory OCCC were enrolled between July 2010 and September 2015, and underwent GPC3 peptide vaccination. Fifteen patients were vaccinated less than six times because their general condition progressively deteriorated, and 17 patients were vaccinated at least six times. Three patients showed a partial response as the best overall response. The GPC3 peptide vaccine induced a GPC3-specific CTL response in 15 out of 24 patients who had PBMCs collected three times or more. The prognosis of palliative care patients without GPC3 peptide vaccinations was significantly poorer than that of those with GPC3 peptide vaccinations (post cancer-treatment survival: p = 0.002). Although the disease control rate was not high, our results suggest that GPC3 peptide vaccinations may hold a significant impact to prolong survival of patients with refractory OCCC, allowing them to maintain quality of life with no serious toxicities.