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

为了研究一种可能的口腔癌免疫基因疗法，我们对人口腔鳞状细胞癌细胞进行了趋化因子和细胞因子转染。基因修饰肿瘤细胞移植nu/nu小鼠的抗肿瘤作用研究。1)将MIP-1α基因连接至质粒表达载体，用脂质法转染hsc -2、-3和-4，检测转染效率。在众多基因转染的克隆中，选择HSC-3/MIP-1α-C7转染到nu/nu小鼠。结果表明，基因修饰的口腔癌移植小鼠具有效应细胞活化和致瘤性。2)利用il -18基因连接腺病毒载体进行二次免疫基因治疗。IL-18isstrongactivatortoNK macrophagesandCTLs。将il -18基因分化的造血干细胞移植到nu/nu小鼠体内，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。通过il -18基因转染的荷瘤小鼠注射重组l -12获得增强的抗肿瘤作用。上述结果表明，趋化因子和细胞因子基因治疗可激发机体先天免疫，具有较强的抗肿瘤作用。该结果也为进一步的口腔癌肿瘤疫苗接种提供了信誉。

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.