Gao Jian-Qing, Tsuda Yasuhiro, Katayama Kazufumi, Nakayama Takashi, Hatanaka Yutaka, Tani Yoichi, Mizuguchi Hiroyuki, Hayakawa Takao, Yoshie Osamu, Tsutsumi Yasuo, Mayumi Tadanori, Nakagawa Shinsaku
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871, Japan.
Cancer Res. 2003 Aug 1;63(15):4420-5.
In this study, we examined antitumor activity of a mouse CC chemokine ILC/CCL27 and a mouse CX(3)C chemokine fractalkine/CX(3)CL1 in vivo. We generated recombinant adenovirus vectors with a fiber mutation, encoding mILC (Ad-RGD-mILC) and mFKN (Ad-RGD-mFKN). We confirmed tumor cells infected with Ad-RGD-mILC and Ad-RGD-mFKN to express and release these chemokines. Tumor rejection experiments in vivo were carried out by inoculating OV-HM cells infected with Ad-RGD-mILC or Ad-RGD-mFKN into immunocompetent mice. mILC significantly suppressed the tumor growth, whereas no such significant effect was observed by mFKN. The antitumor activity induced by mILC was T cell dependent, involving both CD4(+) and CD8(+) T cells. Immunohistochemical analysis revealed accumulation of both CD3(+) lymphocytes and NK cells in the tumor tissue transduced with mILC and mFKN. However, there was a significant difference in the distribution of infiltrating cells. Furthermore, mFKN appeared to have an angiogenic activity, which might have masked its tumor suppressive activity. Collectively, ILC/CCL27 may be a good candidate molecule for cancer gene therapy.
在本研究中，我们检测了小鼠CC趋化因子ILC/CCL27和小鼠CX(3)C趋化因子fractalkine/CX(3)CL1在体内的抗肿瘤活性。我们构建了带有纤维突变的重组腺病毒载体，分别编码小鼠ILC（Ad-RGD-mILC）和小鼠FKN（Ad-RGD-mFKN）。我们证实感染Ad-RGD-mILC和Ad-RGD-mFKN的肿瘤细胞可表达并释放这些趋化因子。通过将感染Ad-RGD-mILC或Ad-RGD-mFKN的OV-HM细胞接种到具有免疫活性的小鼠体内进行体内肿瘤排斥实验。mILC显著抑制了肿瘤生长，而mFKN未观察到这种显著效果。mILC诱导的抗肿瘤活性依赖于T细胞，涉及CD4(+)和CD8(+) T细胞。免疫组织化学分析显示，在用mILC和mFKN转导的肿瘤组织中，CD3(+)淋巴细胞和NK细胞均有聚集。然而，浸润细胞的分布存在显著差异。此外，mFKN似乎具有血管生成活性，这可能掩盖了其肿瘤抑制活性。总体而言，ILC/CCL27可能是癌症基因治疗的一个良好候选分子。
