Significant clinical response of progressive recurrent ovarian clear cell carcinoma to glypican-3-derived peptide vaccine therapy: two case reports.
Significant clinical response of progressive recurrent ovarian clear cell carcinoma to glypican-3-derived peptide vaccine therapy: two case reports.
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DOI：
10.4161/hv.27217
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发表时间：
2014
影响因子：
4.8
通讯作者：
Nakatsura T
中科院分区：
文献类型：
--
作者：
Suzuki S;Shibata K;Kikkawa F;Nakatsura T
癌胚抗原磷脂酰肌醇蛋白聚糖-3（GPC-3）在卵巢透明细胞癌（CCC）中的表达率超过40%，是一个很有前途的免疫靶点。我们先前报道了晚期肝细胞癌（HCC）患者I期临床试验中GPC 3衍生肽疫苗的安全性、免疫学和临床反应。尽管评估了GPC 3衍生肽疫苗对HCC患者的功效，但尚未研究其他GPC 3阳性癌症患者。因此，我们进行了一项II期试验，以评估用GPC 3衍生肽疫苗治疗的卵巢CCC患者的临床结果。GPC 3肽以3 mg/个体的剂量施用。患者接受用不完全弗氏佐剂乳化的GPC 3肽的皮内注射。从第一次注射到第6次注射，每两周进行一次疫苗接种，然后在第7次注射后每6周重复一次。治疗持续至疾病进展。我们在此介绍了两名化疗难治性卵巢癌CCC患者，他们在正在进行的GPC 3肽疫苗试验中获得了显著的临床应答。病例1，一名42岁的晚期复发性卵巢癌患者，伴有肝脏和腹膜后淋巴结转移，接受了HLA-A24限制性GPC 3肽疫苗。第10周的对比增强CT显示使用RECIST标准的部分缓解（PR）。例2为67岁女性，多处淋巴结转移。她注射了HLA-A2限制性GPC 3肽疫苗。根据RECIST，在第37周达到PR。一年多来他们的疾病稳定为我们提供了第一个临床证据，证明基于GPC 3肽的免疫治疗可以显着延长难治性卵巢癌患者的总生存期。
Carcinoembryonic antigen glypican-3 (GPC3) is expressed by >40% of ovarian clear cell carcinoma (CCC) and is a promising immunotherapeutic target. We previously reported the safety of and immunological and clinical responses to a GPC3-derived peptide vaccine in a phase I clinical trial of patients with advanced hepatocellular carcinoma (HCC). Although the efficacy of the GPC3-derived peptide vaccine against HCC patients was evaluated, other GPC3-positive cancer patients have not yet been investigated. Therefore, we conducted a phase II trial to evaluate the clinical outcome of ovarian CCC patients treated with a GPC3-derived peptide vaccine. The GPC3 peptide was administered at a dose of 3 mg per body. Patients received an intradermal injection of the GPC3 peptide emulsified with incomplete Freund’s adjuvant. Vaccinations were performed biweekly from the first until the 6th injection and were then repeated at 6-week intervals after the 7th injection. Treatment continued until disease progression. We herein present two patients with chemotherapy-refractory ovarian CCC who achieved a significant clinical response in an ongoing trial of a GPC3 peptide vaccine. Case 1, a 42-year-old patient with advanced recurrent ovarian CCC with liver and retroperitoneal lymph node metastases, received the HLA-A24-restricted GPC3 peptide vaccine. Contrast-enhanced CT at week 10 revealed a partial response (PR) using RECIST criteria. Case 2 was a 67-year-old female with multiple lymph node metastases. She was injected with the HLA-A2-restricted GPC3 peptide vaccine. According to RECIST, PR was achieved at week 37. The stabilization of their diseases over one year provided us with the first clinical evidence to demonstrate that GPC3 peptide-based immunotherapy may significantly prolong the overall survival of patients with refractory ovarian CCC.
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影响因子：
11.5
作者：
Nakatsura, T;Kageshita, T;Nishimura, Y
通讯作者：
Nishimura, Y
影响因子：
7.5
作者：
Aviel-Ronen, Sarit;Lau, Suzanne K.;Jothy, Serge
通讯作者：
Jothy, Serge
影响因子：
11.5
作者：
Sawada, Yu;Yoshikawa, Toshiaki;Nakatsura, Tetsuya
通讯作者：
Nakatsura, Tetsuya
影响因子：
4.7
作者：
Crotzer, David R.;Sun, Charlotte C.;Gershenson, David M.
通讯作者：
Gershenson, David M.
影响因子：
1.2
作者：
Toretsky, JA;Zitomersky, NL;Schlessinger, D
通讯作者：
Schlessinger, D