CIK细胞作为载体介导重组溶瘤痘病毒rVV-CCL5-SSTR2-Luc+靶向治疗大肠癌的实验研究

大肠癌严重危害人类健康；痘病毒是溶瘤病毒研究热点；静脉注射痘病毒可被免疫系统清除，因此多限于肿瘤内注射，限制了其在大肠癌的应用；将CIK作为载体介导痘病毒经静脉注射治疗大肠癌具临床应用前景；CCL5和SSTR2具强力抗肿瘤作用。本研究拟构建重组溶瘤痘病毒rVV-CCL5-SSTR2-Luc+（rVV），以CIK为载体介导其经静脉注射治疗大肠癌，不仅有效避免rVV被免疫系统清除，将其准确输送至肿瘤，而且当CIK进入体内杀伤肿瘤细胞后，释放出的rVV将发挥二次杀伤肿瘤细胞作用。并且，CCL5高表达将定向诱导T、NK细胞靶向杀伤肿瘤；SSTR2高表达将精确定向并诱导奥曲肽到达肿瘤部位抑制肿瘤生长、诱导肿瘤细胞凋亡；发挥免疫/溶瘤双重协同抗肿瘤作用。研究拟通过体内/外实验评估CIK作为载体介导rVV治疗大肠癌的疗效，探讨其发挥溶瘤效应的作用机制，为应用CIK介导rVV治疗大肠癌奠定实验和理论基础。

Colorectal cancer threaten the healthy of human beings; Vaccinia virus is hotspot in research field of oncolytic virus; Vaccinia virus delivered by intravenous injection can be cleared by immune system, so delievery method of vaccinia virus has been limitid to intratumoral injection mostly, which limited its application in colorectal cancer; Deliver CIK-mediated vaccinia virus by intravenous injection by using CIK cells as vehicles has clinical application prospects in colorectal cancer treatment; CCL5 and SSTR2 have strong anti-tumor effects. In the present study,a vaccinia virus which coexpresses CCL5 and SSTR2 genes - rVV-CCL5-SSTR2-Luc+(rVV) - will be constructed, CIK-mediated rVV will be injected intravenous by using CIK cells as vehicles for targeted colorectal cancer treatment, in this case, rVV can effectively avoid being cleared by immune system, and will be delivered accurately into tumor, after CIK play its roles by killing tumor cells, rVV will be released into tumor cells and play their roles of killing tumor cells secondary time. In addition, high expression level of CCL5 in tumor cells will induce T, NK cells targetting to tumor cells; Meanwhile, the high expression level of SSTR2 in tumor cells will help precise orientation of Octreotide to tumor, which will benefit for the inhibiting of tumor growth and inducing tumor cell apoptosis; CIK-mediated rVV will play the immune / oncolytic double effects. The study aimed to evaluate the therapeutic effect of CIK-mediated rVV in targeted colorectal cancer threatment based on in vitro and in vivo experiments, the mechanisms behind tumor-killing effects will also be explored. This study may be beneficial to estabish the experimental and theoretical basis for the application of CIK-mediated rVV in targeted colorectal cancer threatment.