Park Kyung-Ho, Kim Gyesu, Jang Seung Hun, Kim Cheol Hyeon, Kwon Sung-Youn, Yoo Chul-Gyu, Kim Young Whan, Kwon Hee Chung, Kim Chang-Min, Han Sung Koo, Shim Young-Soo, Lee Choon-Taek
Department of Internal Medicine, Seoul National University College of Medicine, Gene Therapy Laboratory of Clinical Research Institute, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Korea.
Anticancer Res. 2003 Mar-Apr;23(2B):1559-64.
Inadequate release of tumor antigens (TA) and a defective antigen presentation by dendritic cells (DC) are the major mechanisms for how tumor cells can escape the host immune surveillance.
Combined gene therapy of herpes simplex virus thymidine kinase (Tk), GM-CSF and IL-4 via adenoviral vector was tested to solve these problems. After establishing wild-type Lewis lung carcinoma (LLC), vaccinations with LLC transduced with Tk +/- GM-CSF +/- IL-4 were performed.
The LLC-Tk and LLC-Tk-IL-4 vaccination groups failed to suppress the wild-type LLC growth. However, the LLC-Tk-GM-CSF group showed a delayed wild-type tumor growth and LLC-Tk-GM-CSF-IL-4 markedly suppressed tumor growth and increased the survival rate of mice. Immunohistochemistry of the spleen showed a dense infiltration of DCs in the mice treated with LLC-Tk-GM-CSF-IL-4.
Combined gene therapy with Tk-GM-CSF-IL-4 was effective in inducing antitumor immunity by enhancing the DC functions.
肿瘤抗原（TA）释放不足以及树突状细胞（DC）的抗原呈递缺陷是肿瘤细胞逃避宿主免疫监视的主要机制。
测试了通过腺病毒载体联合进行单纯疱疹病毒胸苷激酶（Tk）、粒细胞巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-4（IL-4）的基因治疗来解决这些问题。建立野生型Lewis肺癌（LLC）后，用转导了Tk +/- GM-CSF +/- IL-4的LLC进行疫苗接种。
LLC-Tk和LLC-Tk-IL-4疫苗接种组未能抑制野生型LLC的生长。然而，LLC-Tk-GM-CSF组显示野生型肿瘤生长延迟，LLC-Tk-GM-CSF-IL-4显著抑制肿瘤生长并提高了小鼠的存活率。脾脏免疫组化显示，用LLC-Tk-GM-CSF-IL-4处理的小鼠中DC有密集浸润。
Tk-GM-CSF-IL-4联合基因治疗通过增强DC功能在诱导抗肿瘤免疫方面有效。
