一般演題

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肝癌選択的な遺伝子治療を目指して〜癌特異的な傷害効果を持つ組みかえアデノウイルスの作成：立石敬介¹,金井文彦¹,大橋誠¹,白鳥康史¹,吉田陽子²,濱田洋文²,小俣政男¹（¹東京大学・消化器内科,²癌研・癌化学療法センター・分子生物治療研究部）

Tumor specific replication competent adenovirus ; specific and effective gene therapy against hepatocellular carcinoma：Keisuke TATEISHI¹, Fumihiko KANAI¹, Makoto OHASHI¹, Yasushi SHIRATORI, Yoko YOSHIDA², Hirofumi HAMADA², Masao OMATA¹ (¹2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo., ²Department of Molecular Biotherapy Research, Cancer Chemotherapy Center, Cancer Institute, Japanese Foundation for Cancer Research.)

An attenuated adenovirus is known to be replicated in p53-deficient human tumor cells. To clarify the specific replication in the hepatocellular carcinoma (HCC), we constructed an E1B deleted adenovirus, in which E1A could be induced by the α-fetoprotein (AFP) transcriptional regulatory region. Furthermore the cytopathic effects (CPE) of the virus against several HCC cell lines were examined in vitro as well as in vivo. The expression of EIA gene was examined by westernblot. Viral replication was examined by the titration of virus in the culture medium, and its CPE were examined by MTT assay. Subcutaneous tumors of Hep3B (AFP(+), p53 mutant) or HLF (AFP(-), p53 wild) were established in nude mice, and the ability to supress tumor growth is analyzed. Both the replication of AdAFP-E1AdB and the CPE were documented in all AFP (+) cells when infected, and not in the AFP (-) cells. In the case of HCC with the wild-type p53, like HepG2 (AFP(+)), the viral replication was also detected. AdAFP-E1AdB replicates in the AFP(+) HCC cells, and has a possibility for tumor specific gene therapy of HCC.