Study of immuno-tolerance for digestive cancer and tumor specific immunotherapy using autologous cancer cells as immunogens

消化道癌免疫耐受研究及以自体癌细胞为免疫原的肿瘤特异性免疫治疗

• 批准号: 12671289
• 负责人: SOUDA Hiroaki
• 金额: $ 0.83万
• 依托单位: Chiba Cancer Center Research Institute
• 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 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671289/
• 关键词: cytotoxic T lymphocytes; mixed lymphocytes and tumor culture; Th1 CD4 + T lymphocyte; solved IL-2 receptor; Th1 CD4^+Tリンパ球; 可溶性IL-2レセプタター; Th1; CD4^+Tリンパ球

I had studied tumor specific immunotherapy for digestive cancer using cytotoxic T lymphocytes (CTLs). From my clinical efficacies I thought that the immuno-tolerance for cancer was existed in far advanced cancer patients. I investigated cytokine in vivo of far advanced cancer patients and cytokines in vitro for induction of CTLs. I collected ascites from 10 patients with carcinomatous peritonitis and 10 samples of exudation from drainage after curative operation. I investigated IL-2, IL-12, IFN gamma, IL-4, IL-6, and IL-10.The cytokines of Th1 were low level in two groups and the cytokines of Th2, IL-4 and IL-6 were high level, however, IL-10 level were irregular. The solved IL-2 receptor (sIL-2R) in peripheral blood plasma and ascites with carcinomatous peritonitis were investigated. The levels of sIL-2R were high in ascites from carcinomatous peritonitis patients and plasma from patients with M factors. I attempted to induce CTLs from peripheral blood mononuclear cells by 2 steps MLTC technique, using alternative pathway for autologous cancer cells as the immunogen. In my data of cytokines in MLTC, the number of CD14^<+> has a serious influence upon the differentiation CD4^<+> T lymphocytes that have a major role for the induction of CTLs. I attempted the adoptive immunotherapy using activated CTLs in vitro for patients with far advanced colon cancer, who have no efficacy by other therapies and whose autologous cancer cell lines were established. The clinical efficacies were minor responses.

我曾研究过使用细胞毒性T淋巴细胞(CTL)治疗消化道癌的肿瘤特异性免疫疗法。从我的临床疗效来看，我认为晚期癌症患者存在对癌症的免疫耐受。我研究了晚期癌症患者体内的细胞因子和体外诱导CTL的细胞因子。我收集了10例癌性腹膜炎患者的腹水和10例根治性手术后引流液样。检测IL-2、IL-12、干扰素-γ、IL-4、IL-6、IL-10。两组患者Th1细胞因子水平较低，Th2、IL-4、IL-6细胞因子水平较高，而IL-10水平无明显变化。检测癌性腹膜炎患者外周血和腹水中可溶性白介素2受体(sIL-2R)水平。癌性腹膜炎患者的腹水和M因子阳性患者的血浆中sIL-2R水平较高。本研究以自体癌细胞替代途径为免疫原，尝试用两步MLTC技术从外周血单个核细胞中诱导CTL。在我对MLTC细胞因子的研究中，CD14^&lt；+&gt；T淋巴细胞的数量对其分化有严重影响，而CD14^&lt；+&gt；T淋巴细胞在CTL的诱导中起主要作用。我尝试了用激活的CTL进行体外过继免疫治疗，用于晚期结肠癌患者，这些患者用其他方法治疗无效，并且建立了自体癌细胞系。临床疗效均为轻微反应。