Attempts to develop a novel cell therapy system for chromic viral infections and non-viral tumors.

我们利用新培育的NOG小鼠对病毒诱导的疾病(HTLV-I/ATL、HIV-I/AIDS和EBV/AIDS相关淋巴瘤)和非病毒诱导的癌症进行了形态学、遗传学和分子水平的研究。我们最初使用无条件NOG小鼠建立了一种新的ATL动物模型。我们还展示了几种新开发的核因子-kB抑制剂的效果。我们证明了NK细胞在NOG小鼠和乳腺癌患者中的有效性和安全性。我们还通过移植人脐带血来源的造血干细胞构建了人源化的NOG小鼠，这些干细胞最终发育为人类B细胞、T细胞和其他与淋巴组织中淋巴滤泡样结构生成相关的单核/巨噬细胞和树突状细胞。该系统允许HIV-1和EBV的长期感染和人类免疫反应。所有这些数据表明，NOG小鼠可能有潜力成为一种有用的动物模型，用于开发新的治疗方案，以对抗各种人类起源的传染病和癌症。

Our efforts have been made regarding morphological, genetic and molecular studies on virally-induced diseases (HTLV-I/ATL, HIV-I/AIDS, and EBV/AIDS-associated lymphoma) and non-virally induced cancers using newly developed NOG mice. We initially established a novel animal model for ATL using unconditional NOG mice. We also showed the effect of several newly developed NF-kB inhibitors. We proved efficacy and safety of NK cells in NOG mice as well as in the breast tumor-bearing patients. We also constructed humanized NOG mice by transplanting human cord blood-derived hematopoietic stem cells that eventually developed into human B cells, T cells and other monocytes/macrophages and dendritic cells associated with the generation of lymphoid follicle-like structures in lymphoid tissues. This system allows a long-lasting infection of both HIV-1 and EBV with human immune responses. All these data suggest that NOG mice may have potential as a useful animal model for the development of new regimen against various infectious diseases and cancers of human origin.