恶性肿瘤严重危害人类健康。以机体免疫细胞为主体的细胞免疫治疗，以其强大的抗肿瘤作用和较低的毒副作用逐步成为肿瘤治疗研究的新方向。研究显示膜结合性的补体调节蛋白(mCRPs) CD46可使肿瘤细胞逃避机体的免疫防御。人35型腺病毒(Ad35)主要感染表达CD46 的细胞，而突变Ad35纤维突蛋白（Ad35K++）比野生型Ad35K对CD46有更强的亲和力。我们已成功构建和制备了重组人Ad35K++蛋白，并通过体外实验证明Ad35K++蛋白可以促进NK细胞的杀伤功能。拟在此基础上，观察Ad35K++蛋白抑制CD46分子后，肿瘤细胞增殖、凋亡的变化，以及肿瘤细胞对NK细胞杀伤敏感性的改变；同时探讨Ad35K++蛋白通过Notch信号通路诱导NK细胞杀伤功能的分子机制，并在体内动物模型中验证Ad35K++蛋白提高NK细胞抗肿瘤效应，为临床NK细胞过继免疫治疗肿瘤提供新的有效策略。

As a frequently occurring disease, malignant tumors have a great threat to human health. Immunotherapy has become the latest anti-cancer biological science. Many tumors upregulate expression of CD46 to escape destruction by immune defense. Selected from the expression library of adenovirus type 35 fiber knob mutants, a variant (Ad35K++) that had a higher affinity to CD46 than did the natural Ad35 fiber knob. We have successfully produced recombinant human Ad35K++ protein, and demonstrated that Ad35K++ could up-regulate the cytotoxicity of NK cells by in vitro experiments. On this basis, we want to investigate after Ad35K++ inhibits the expression of CD46, changes of proliferation and apoptosis in tumor cells, and the sensitivity of tumor cells to NK cells. Futhermore, we want to explore whether Ad35K++ induced NK cell function by Notch signaling pathway, and study the molecular mechanisms in animal models. With the enhancement of anti-tumor impact of NK cells, we could explore the potential of NK cells for adaptive immunotherapy.