Studies on Treatment Effects and Prognoses of Adoptive Immunotherapy of Cancer Patients by using autologous and allogeneic lymphocytes.

使用自体和同种异体淋巴细胞对癌症患者进行过继免疫治疗的治疗效果和预后的研究。

• 批准号: 06671888
• 负责人: KUBOTA Eiro
• 金额: $ 1.22万
• 依托单位: Kanagawa Dental College (1995)佐賀医科大学 (1994)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671888/
• 关键词: head and neck cancer; adoptive immunotherapy; allogeneic spleen cells; killer cells; anti-tumor cytokines; RT-PCR technique; 頭頸部癌

Culture of peripheral blood mononuclear cells (PBMC) with a heat and penicillin-treated streptococcal preparation, OK-432, has induced effector cells which have both cell-mediated and cytokine-mediated antitumor activities. We performed locoregional adoptive immunotherapy (AIT) with OK-432-activated PBMC (OKMC) in head and neck cancer patients as a part of preoperative treatment. In the present study we evaluated the correlation of tumor mononuclear cell infiltration and patient's prognosis. The AIT group (10 cases) was more abundant in infiltrating T cells (UCHL-1+) in tumor tissue than those of the non-AIT group (10 cases). There were three recurrences out of 10 cases of AIT group, in which a small number of OKMC was transferred and had much less T cell infiltration of the tumor parenchyma.Tumor tissues were surgically excised and therapeutic effect was examined histologically. In AIT group, focal necrosis of cancer tissue was observed at the site of OKMC injection especially at the portion of massive infiltration of mononuclear cells. These cell death was characteristic of apoptosis as examined by HE and immunohistochemical staining with anti-Le^y antibody. Various kind of cytokine mRNAs including IL-1, TNFalpha, IL-6, IFNgamma, IL-2, IL-4 were also detected in the tumor burden by RT-PCR technique. The IL-1 and IL-2 mRNA were detected in almost all of the tumor tissue, but IFNgamma was found only in 50% of these cases. Furthermore, tumor tissue which lack the IFNgamma message was unequivocally expressed immunosuppressive cytokine IL-10. The IFNgammamRNA was reappeared after the AIT in the tumor tissue which could not be detected its message before AIT.The above mentioned phenomena were presumed to be direct effect of AIT.Thus, it is considered that local administration of OKMC could be one of the most feasible BRM therapies in head and neck cancers.

用加热和青霉素处理的链球菌制剂OK-432培养外周血单个核细胞(PBMC)，可以诱导出既具有细胞介导的抗肿瘤活性又具有细胞因子介导的抗肿瘤活性的效应细胞。作为术前治疗的一部分，我们对头颈癌患者进行了OK-432激活的PBMC(OKMC)局部区域过继免疫治疗(AIT)。在本研究中，我们评估了肿瘤单个核细胞浸润与患者预后的关系。AIT组(10例)肿瘤组织中UCHL-1+T细胞较非AIT组(10例)明显增多。AIT组10例中有3例复发，转移少量OKMC，肿瘤实质T细胞浸润明显减少，手术切除肿瘤组织，观察疗效。AIT组注射OKMC后可见癌组织灶性坏死，尤以单核细胞大量浸润区更为明显。HE染色和抗Le^y抗体免疫组织化学染色显示，这些细胞死亡为细胞凋亡的特征。RT-PCR法检测肿瘤组织中IL-1、TNFα、IL-6、IFN-γ、IL-2、IL-4等多种细胞因子的表达。IL-1和IL-2mRNA在几乎所有的肿瘤组织中都有表达，但只有50%的肿瘤组织中有干扰素-γ的表达。此外，缺乏IFNGamma信息的肿瘤组织明确表达免疫抑制细胞因子IL-10。肿瘤组织中IFNGammaRNA在AIT后重新出现，在AIT前检测不到其信息，推测上述现象可能是AIT的直接作用，因此认为局部应用OKMC可能是头颈部肿瘤BRM治疗最可行的方法之一。

项目成果

Katano M: "Inhibition of fumor cell growth by a human B-cell line" Biotherapy. 8. 1-6 (1995)

Katano M：“人类 B 细胞系抑制肿瘤细胞生长”生物疗法。

Hu ZL: "Effective induction of human NK cells with OK-432 and further augmentation of their cytolytic function by rIL-2" Microbiol Immunol. 38. 183-190 (1994)

Hu ZL：“用 OK-432 有效诱导人类 NK 细胞，并通过 rIL-2 进一步增强其细胞溶解功能”Microbiol Immunol。

Katano M,Matsuo T,Morisaki T,Naito K,Nagumo F,Kubota E,Nakamura M,Hisatsugu T,and Tadano J: "Increased proliferation of a human breast carcinoma cell line by recombinant interleukin-2." Cancer Immunol Immunother. 39. 161-166 (1994)

Katano M、Matsuo T、Morisaki T、Naito K、Nagumo F、Kubota E、Nakamura M、Hisatsugu T 和 Tadano J：“通过重组白细胞介素 2 增加人乳腺癌细胞系的增殖。”

Katano M,Kubota E,Nagumo F,Matsuo T,Hisatsugu T,and Tadano J: "Inhibition of tumor cell growth by a human B-cell line" Biotherapy. 8. 1-6 (1995)

Katano M、Kubota E、Nagumo F、Matsuo T、Hisatsugu T 和 Tadano J：“人类 B 细胞系对肿瘤细胞生长的抑制”生物疗法。

Katano M,Matsuo T,Morisaki T,Naito K,Nagumo F,Kubota E,Nakamura M,Hisatsugu T,and Tadano J: "Increased proliferation of a human breast carcinoma cell line by recombinant interleukin-2" Cancer Immunol Immunother. 39. 161-166 (1995)

Katano M、Matsuo T、Morisaki T、Naito K、Nagumo F、Kubota E、Nakamura M、Hisatsugu T 和 Tadano J：“通过重组白细胞介素 2 增加人乳腺癌细胞系的增殖”癌症免疫免疫疗法。