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首页> 外文期刊>Esophagus >Phase I clinical trial of vaccination with URLClO-derived peptide for patients with advanced esophageal cancer
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Phase I clinical trial of vaccination with URLClO-derived peptide for patients with advanced esophageal cancer

机译：用URLC10衍生肽疫苗接种治疗晚期食管癌的I期临床试验

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Background Up-regulated gene in lung cancer 10 (URLC10), confirmed to be lymphocyte antigen 6 complex locus K and defined as an oncoantigen, has been identified as a tumor-associated antigen by systematic analysis of expression levels of thousands of genes in lung cancer tissues and esophageal squamous cell carcinoma tissues, which were compared with those of normal human tissues by use of cDNA microarray analysis. Human leukocyte antigen (HLA)-A*2402-positive dendritic cells pulsed with URLClO-derived epitope peptide induced CD8+ cytotoxic T lymphocytes to exert specific cytotoxicity against the HLA-A*2402-positive URLClO-expressing esophageal carcinoma cell Lines.Methods In a phase I clinical trial we evaluated the safety and immunogenicity of a URLC10-177 peptide vaccine emulsified with Montanide ISA51 for patients with unresectable advanced esophageal cancer. One milligram of URLC10-177 peptide in 1 mL sterile saline was emulsified with 1 mL incomplete Freund's adjuvant and administered subcutaneously to the inguinal region or axilla of the patients. One course of treatment comprised four vaccinations, which were performed every week in the first and second treatment courses and subsequently every 2 weeks after the first vaccination in the third treatment course.Results Redness and induration of the skin were the only adverse events at the injection site and were believed to be a delayed-type hypersensitivity (DTH) reaction against the peptide vaccine. A URLC10-177-specific immune reaction in the enzyme-linked immunospot assay was detected in three of four DTH-positive patients (75 %) and in one of three DTH-negative patients (33 %). Furthermore, patients who had a DTH reaction seemed to survive longer than those who had no DTH reaction.Conclusion URLClO-177 peptide/Montanide vaccine therapy was well tolerated and induced a URLClO-177 peptide-specific immune response. Therapeutic URLClO-177 peptide vaccination is expected to have clinical benefit in prolonging the survival of patients with unresectable advanced esophageal cancer.
机译：背景肺癌10（URLC10）中的上调基因已被确认为淋巴细胞抗原6复杂基因座K，并被定义为癌抗原，通过系统分析肺癌中数千个基因的表达水平，已将其鉴定为肿瘤相关抗原。组织和食管鳞状细胞癌组织，通过使用cDNA微阵列分析与正常人组织进行比较。用URLC10衍生的表位肽脉冲的人白细胞抗原（HLA）-A * 2402阳性树突细胞诱导CD8 +细胞毒性T淋巴细胞对表达HLA-A * 2402阳性URLC10O的食道癌细胞系产生特异性细胞毒性。 I期临床试验我们评估了用Montanide ISA51乳化的URLC10-177肽疫苗对无法切除的晚期食管癌患者的安全性和免疫原性。用1 mL不完全弗氏佐剂乳化1 mL无菌盐水中的1毫克URLC10-177肽，并皮下注射至患者的腹股沟区域或腋窝。一个疗程包括四个疫苗接种，分别在第一和第二个疗程中每周进行一次，随后在第二个疗程中的第一次疫苗接种后每两周进行一次。结果皮肤红肿和硬结是注射时唯一的不良事件位点，被认为是针对肽疫苗的迟发型超敏反应。在酶联免疫斑点测定中，在四名DTH阳性患者中有三名（75％）和三名DTH阴性患者之一（33％）中检测到URLC10-177特异性免疫反应。此外，发生DTH反应的患者似乎比没有DTH反应的患者存活更长。结论URLC10-177肽/ Montanide疫苗疗法耐受性良好，可诱导URLC10-177肽特异性免疫反应。预期治疗性URLC10-177肽疫苗的接种在延长不能切除的晚期食道癌患者的生存中具有临床益处。

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