Tominaga M, Iwashita Y, Ohta M, Shibata K, Ishio T, Ohmori N, Goto T, Sato S, Kitano S
Department of Surgery I, Oita University Faculty of Medicine, Yufu, Oita, Japan.
Cancer Gene Ther. 2007 Aug;14(8):696-705. doi: 10.1038/sj.cgt.7701059. Epub 2007 May 18.
The number of tumor-infiltrating lymphocytes is known to be related to outcomes in patients with a variety of malignancies. Interferon (IFN) gamma-inducible protein-10 (IP-10) and monokine induced by IFNgamma (MIG) have chemotactic effects on activated T lymphocytes and natural killer (NK) cells. The aim of this study was to evaluate the antitumor effects of exogenous expression of the MIG and IP-10 genes delivered to solid tumors by poly [D,L-2,4-diaminobutyric acid] (PDBA). The murine MIG and IP-10 genes were transfected into mouse neuroblastoma cells with PDBA. MIG and IP-10 levels in supernatants of transfected cells were measured by enzyme-linked immunosorbent assay. The chemotactic activities of MIG and IP-10 in the supernatants of cell cultures were measured by chemotaxis assay. Tumors were injected in vivo with PDBA/pmMIGColon, two colonsIP-10 complexes to evaluate the effects of these genes on tumor volume and survival time of mice. Transfected PDBA/pmMIGColon, two colonsIP-10 complexes produced MIG and IP-10 protein in vitro. MIG and IP-10 proteins secreted into the culture medium showed chemotactic activity. MIG and IP-10 gene therapy with the PDBA system in vivo significantly inhibited tumor growth and prolonged survival time of mice. In conclusion, PDBA-mediated MIG and IP-10 gene therapy may be useful for treatment of solid tumors.
已知肿瘤浸润淋巴细胞的数量与多种恶性肿瘤患者的预后相关。干扰素（IFN）γ诱导蛋白10（IP - 10）和IFNγ诱导的单核细胞趋化蛋白（MIG）对活化的T淋巴细胞和自然杀伤（NK）细胞具有趋化作用。本研究的目的是评估通过聚[D，L - 2,4 - 二氨基丁酸]（PDBA）将MIG和IP - 10基因外源性表达递送至实体瘤的抗肿瘤作用。将小鼠MIG和IP - 10基因用PDBA转染到小鼠神经母细胞瘤细胞中。通过酶联免疫吸附测定法测量转染细胞上清液中的MIG和IP - 10水平。通过趋化性测定法测量细胞培养上清液中MIG和IP - 10的趋化活性。将PDBA/pmMIG结肠、双结肠IP - 10复合物体内注射到肿瘤中，以评估这些基因对小鼠肿瘤体积和生存时间的影响。转染的PDBA/pmMIG结肠、双结肠IP - 10复合物在体外产生MIG和IP - 10蛋白。分泌到培养基中的MIG和IP - 10蛋白表现出趋化活性。体内应用PDBA系统进行MIG和IP - 10基因治疗可显著抑制肿瘤生长并延长小鼠的生存时间。总之，PDBA介导的MIG和IP - 10基因治疗可能对实体瘤的治疗有用。
