Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer
Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer
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DOI：
10.1111/j.1349-7006.2009.01200.x
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发表时间：
2009-08-01
期刊：
影响因子：
5.7
通讯作者：
Fujii, Hideki
中科院分区：
文献类型：
--
作者：
Kono, Koji;Mizukami, Yoshiki;Fujii, Hideki
我们先前鉴定了三种新的hla - a24限制性表位肽，它们来源于三种癌-前列腺抗原，TTK蛋白激酶（TTK），淋巴细胞抗原6复合物位点K （LY6K）和胰岛素样生长因子(IGF)-II mRNA结合蛋白3 (IMP-3)，作为预防食管鳞状细胞癌（ESCC）的癌症疫苗的靶点。为了检验这三种多肽联合疫苗治疗的安全性、免疫原性和抗肿瘤效果，10名hla - a2402阳性的晚期ESCC患者参加了一项I期临床试验，这些患者未能接受标准治疗。三种肽（每一种1毫克）与1毫升不完全弗氏佐剂一起在颈部三个不同的区域进行皮内注射，每周持续5周。癌症疫苗治疗耐受性良好，没有任何与治疗相关的3级或4级不良事件。通过酶联免疫斑点法观察10例ESCC患者接种疫苗后9例外周血淋巴细胞的TTK-、LY6K-和/或imp -3特异性t细胞免疫反应。接种疫苗后的中位生存时间为6.6个月。在10例患者中，50%的人接种疫苗后可产生良好的临床反应。1例肝转移完全缓解持续7个月，1例所有肺转移病灶均客观缓解，3例病情稳定至少2.5个月。这三种多肽的肿瘤疫苗治疗表现出令人满意的安全性和良好的免疫原性以及良好的疾病控制率，值得进一步的临床研究。（癌症科学2009）。
We previously identified three novel HLA-A24-restricted epitope peptides, which were derived from three cancer-testis antigens, TTK protein kinase (TTK), lymphocyte antigen 6 complex locus K (LY6K), and insulin-like growth factor (IGF)-II mRNA binding protein 3 (IMP-3), as targets for cancer vaccination against esophageal squamous cell carcinoma (ESCC). To examine the safety, immunogenicity, and antitumor effect of vaccine treatment using a combination of these three peptides, 10 HLA-A2402-positive advanced ESCC patients who failed to standard therapy were enrolled in a phase I clinical trial. Each of the three peptides (1 mg each) was intradermally administered with 1 mL of incomplete Freund's adjuvant to the neck in three separate regions weekly for 5 weeks. The cancer vaccination therapy was well tolerated without any treatment-associated adverse events of grade 3 or 4. The TTK-, LY6K-, and/or IMP-3-specific T-cell immune responses were observed by enzyme-linked immunospot assay in peripheral blood lymphocytes obtained from nine of the 10 ESCC patients after their vaccination. The median survival time after the vaccination was 6.6 months. The vaccination could induce good clinical responses in 50% of the 10 patients. One patient experienced a complete response in hepatic metastasis lasting 7 months, one showed objective responses in all lung metastasis lesions, and three patients revealed a stable disease condition for at least 2.5 months. The cancer vaccine therapy using these three peptides demonstrated satisfactory safety and good immunogenicity as well as promising disease control rate, and therefore warrants further clinical studies. (Cancer Sci 2009).