The development of new therapy for digestive organ solid cancer using fibroblasts genetically engineered to produce cytokine combined with anti-platelet agents

化疗与免疫治疗相结合是治疗消化系统实体瘤等抗原性低的难治性肿瘤的理想方案。首先，我们利用小鼠胰腺癌细胞系PAN02建立了小鼠胰腺癌肝转移模型。我们还研究了吉西他滨联合IL-2门静脉注射对肝转移形成的影响。结果表明，吉西他滨+IL-2联合治疗对小鼠肝转移瘤肝重量和肝转移数目的保护作用明显优于对照组、吉西他滨单独用药组和IL-2单独用药组。此外，当IL-2注射到脾(门脉系统)而不是腹部(全身给药)时，IL-2更能增强吉西他滨的保护作用。与对照组相比，吉西他滨+IL-2组肝转移瘤的病理组织学发现淋巴细胞明显增多。此外，作为一种门脉注射IL-2的模型，我们正在研究基因工程成纤维细胞在该模型中表达IL-2的有效性。

The combination of chemotherapy with immune therapy is desirable for intractable and low antigenicity tumor such as digestive organ solid cancer. At first, we made hepatic metastasis model of pancreatic carcinoma in laboratory mouse using a murine pancreatic carcinoma cell line, PAN02. And we studied combined effects of gemcitabine with IL-2 injected into a portal vein on the formation of liver metastasis. As a result, the combined therapy of gemcitabine + IL-2 showed more significant protective effect on liver metastasis in liver weight and the number of the hepatic metastasis, compared to the control group, the gemcitabine alone group, and IL-2 alone group. Furthermore, IL-2 more strongly enhanced the protective effect of gemcitabine when IL-2 was injected into spleen (a portal system) not into abdomen (systemic administration). Lymphocytes were significantly found in pathologic findings of a liver metastasis in the group of gemcitabine + IL-2 in comparison with the control group. Moreover, as a portal injection model of IL-2, we are studying the effectiveness of fibroblasts genetically engineered to express IL-2 in this murine model.