Development of cancer vaccine therapy targeting CEA and the analysis of its immunologicai responses

针对CEA的癌症疫苗疗法的开发及其免疫反应分析

• 批准号: 12671252
• 负责人: UCHIYAMA Kazuhisa
• 金额: $ 1.92万
• 依托单位: Wakayama medical school
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671252/
• 关键词: CEA; CTL; DC; ELISPOT; Tetramer; 腫瘍特異的受動免疫治療; 樹状細胞; CEAペプチド; 樹状細胞(DC); ELISPOT法; テトラマー

Carcinoembryonic antigen (CEA) is strongly expressed in vast majority of gastrointestinal malignancies. Recently several epitope peptides derived from CEA were identified. It was already clarified HLA-A24 restricted peptide CEA652[9] (TYACFVSNL) was capable of eliciting specific CTL which could lyse tumor cells expressing HLA-A24 and CEA. HLA-A24 is the most applicable MHC class I allele in Japanese. In this pilot study, we used peptide pulsed dendritic cells (DCs) generated from peripheral blood mononuclear cells supplemented with GM-CSF and IL-4. Eight patients with advanced CEA expressing gastrointestinal malignancies received every 2 or 3 weeks subcutaneous vaccination. Changes in CTL reactivity after vaccinations were assessed by enzyme-linked immunospot (ELISPOT) assay and their capacity to elicit anti-tumor CTL in vitro. Three of six patients developed their CTL reactivity after vaccinations. Two of six patients responded in ELISPOT assay. DTH reaction was observed in one of eight patients at the injected site. Skin biopsy at the injected site demonstrated infiltration of lymphocytes. However no major tumor regressions were observed. No significant toxic adverse effects were observed except mild diarrhea in one case after three times vaccination. In conclusion, our results demonstrated that peptide pulsed DCs injected subcutaneously was safe and could develop peptide specific CTL activity in cancer pattante.

癌胚抗原（CEA）在绝大多数胃肠道恶性肿瘤中强烈表达。最近鉴定了几个源自 CEA 的表位肽。已经阐明 HLA-A24 限制性肽 CEA652[9] (TYACFVSNL) 能够引发特异性 CTL，从而裂解表达 HLA-A24 和 CEA 的肿瘤细胞。 HLA-A24 是日语中最适用的 MHC I 类等位基因。在这项初步研究中，我们使用了由补充有 GM-CSF 和 IL-4 的外周血单核细胞产生的肽脉冲树突状细胞 (DC)。 8 名患有晚期 CEA 表达胃肠道恶性肿瘤的患者每 2 或 3 周接受一次皮下疫苗接种。通过酶联免疫斑点 (ELISPOT) 测定评估疫苗接种后 CTL 反应性的变化及其在体外引发抗肿瘤 CTL 的能力。六名患者中的三名在接种疫苗后出现了 CTL 反应性。六名患者中有两名在 ELISPOT 检测中有反应。八名患者中的一名在注射部位观察到 DTH 反应。注射部位的皮肤活检显示淋巴细胞浸润。然而，没有观察到主要的肿瘤消退。接种3次后除1例轻度腹泻外，未见明显毒副反应。总之，我们的结果表明皮下注射肽脉冲 DC 是安全的，并且可以在癌症帕坦特中产生肽特异性 CTL 活性。

项目成果

Uchiyama K.: "Indication and Procedure for Treatment of Hepatolithiasis"Arch.Surg.. 137(2). 149-153 (2002)

Uchiyama K.：“肝结石治疗的适应症和程序”Arch.Surg. 137(2)。

Uchiyama K.: "Timing of lcperoscopiccholecy rectory for acute chelecystitis with cluley stolithisis"Hepato-Gastroenterology. 49. (2003)

Uchiyama K.：“胆囊镜胆囊切除术治疗急性胆囊炎伴杂石症的时机”肝胃肠病学。

Uchiyama K, Onishi H, Tani M, Kinoshita H, Ueno M, Yamaue H: "Indication and procedure for treatment of hepatolithiasis"Arch Surg. 137(2). 149-153 (2002)

Uchiyama K、Onishi H、Tani M、Kinoshita H、Ueno M、Yamaue H：“肝内胆管结石治疗的适应症和程序”Arch Surg。

Kazuhisa Uchiyama: "Indication and procedure for treatment of hepatolithiasis"Arch Surg. 137. 149-153 (2002)

Kazuhisa Uchiyama：“肝内胆管结石治疗的适应症和程序”Arch Surg。

Uchiyama K.: "Long-term prognosis after treatment of patients with choledocholithiasis"Ann.Sung.. 235. (2003)

Uchiyama K.：“胆总管结石患者治疗后的长期预后”Ann.Sung.. 235. (2003)