Evaluation of immunoffector cells in combination gene therapy of IL-18 and IL-12

免疫效应细胞在IL-18和IL-12联合基因治疗中的评价

• 批准号: 15592142
• 负责人: MIYAKE Mashiko
• 金额: $ 2.18万
• 依托单位: Nihon University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15592142/
• 关键词: gene therapy; oral cancer; MIP-1α; IL-18; ICE; IL-12; nu; nu mouse; adenovirus vector; genetherapy; IL12; PAM212; macrophage; Killer Tcell; 口腔癌遺伝子治療; 扁平上皮癌; マウス

To investigate a possible immuno-genetherapyfororalcancer, weperformedchemokineandcytokinegene transfection to human oral squamous cell carcinoma cells. Anti-tumor effects studied by the gene-modified tumor cells transplant the nu/nu mice. 1) MIP-1α gene ligated into plasmidexpression vector and transfected with lipofection methodintoHSC-2,-3and-4-fortestingtrasfectionefficiency. Of numerous gene-transfected clones, HSC-3/MIP-1α-C7 was selected and transfected to nu/nu mice. The result indicated that activation of effecter cells and tumorigenecity wereidentifiedinthose gene modified oral cancer transplanted mice. 2) Second immno-genetherapyperformedusingIL-18gene ligated adenovirusvector. IL-18isstrongactivatortoNK, macrophagesandCTLs. IL-18genemodifiedHSCcellswere transplanted to nu/nu mice, which demonstrated reduction of tumor volume compared with control tumor transplantation. But the tumor did not completely regressed from the inoculation site. An augmented antitumor effectwasobtainedbyrecombinantIL-12injectiontotheIL-18genetransfectiontumor bearing mice. Above result indicated that chemokines and cytokine gene therapy excites the innate immunity and possessed strong antitumor effect. The result gives also credit for further tumor vaccination of oral cancer.

为探讨免疫基因治疗口腔癌的可能性，我们对人口腔鳞癌细胞进行了趋化因子基因和精氨酸基因的转染。转基因肿瘤细胞移植nu/nu小鼠的抗肿瘤作用研究。1)将MIP-1α基因连接到质粒表达载体中，用脂质体法转染HSC-2、-3和-4，检测转染效率。在众多的基因转染克隆中，选择HSC-3/MIP-1α-C7并转染nu/nu小鼠。结果表明，经基因修饰的口腔癌移植瘤小鼠体内存在效应细胞的激活和致瘤性。2)用IL-18基因连接腺病毒载体进行第二次免疫基因治疗。IL-18是NK、巨噬细胞和CTL的强激活剂。将IL-18基因修饰的HSC细胞移植到nu/nu小鼠，与对照肿瘤移植相比，肿瘤体积减小。但肿瘤并没有从接种部位完全消退。重组IL-12对IL-18基因转染的荷瘤小鼠有增强的抗肿瘤作用。以上结果表明，趋化因子和细胞因子基因治疗可激发机体天然免疫，具有较强的抗肿瘤作用。该结果也为口腔癌的进一步肿瘤疫苗接种提供了依据。