Iida Tomonori, Shiba Hiroaki, Misawa Takeyuki, Ohashi Toya, Eto Yoshikatsu, Yanaga Katsuhiko
Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan.
Cancer Sci. 2008 Oct;99(10):2097-103. doi: 10.1111/j.1349-7006.2008.00953.x.
Adenoviral-vector expressing CD40L (AxCAmCD40L)-mediated gene therapy was studied for treatment of hepatocellular carcinoma (HCC) using CD40 ligand (CD40L) complementary DNA in rats. The particular focus was whether humoral immunity took part in antitumor effect. When tumor cells transduced by AxCAmCD40L were implanted into the subcutaneous tissues of syngeneic rats, the tumor growth was suppressed. Intratumoral injection of AxCAmCD40L to pre-existing tumor in rats also led to significant reduction of tumor size. When tumor cells were re-implanted to prevention model rats and treatment model rats, no tumor growth was observed. Many studies to date have reported that cellular immunity induces antitumor immunity. However, the present study demonstrated that not only cellular immunity but also humoral immunity plays an essential role in a HCC model. These observations suggested that CD40L-mediated immune gene therapy for HCC was very effective treatment by activation of both cellular and humoral immune system.
利用大鼠体内的CD40配体（CD40L）互补DNA，研究了表达CD40L的腺病毒载体（AxCAmCD40L）介导的基因疗法对肝细胞癌（HCC）的治疗效果。特别关注的是体液免疫是否参与了抗肿瘤作用。当将经AxCAmCD40L转导的肿瘤细胞植入同基因大鼠的皮下组织时，肿瘤生长受到抑制。向大鼠已有的肿瘤内注射AxCAmCD40L也导致肿瘤大小显著减小。当将肿瘤细胞重新植入预防模型大鼠和治疗模型大鼠体内时，未观察到肿瘤生长。迄今为止，许多研究报告称细胞免疫可诱导抗肿瘤免疫。然而，本研究表明，在肝癌模型中，不仅细胞免疫，体液免疫也起着至关重要的作用。这些观察结果表明，CD40L介导的肝癌免疫基因疗法通过激活细胞和体液免疫系统，是一种非常有效的治疗方法。
