RECOMBINANT HUMAN CC10 AND NOTCH-1 ANTAGONIST IN NSCLC

这项拟议研究的目的是评估两种潜在抗肿瘤药物单独和联合在肺癌过继转移模型中的有效性。第一种药物是重组人CC 10，最近已显示其在体外对多种人肿瘤细胞类型具有抗转移和肿瘤抑制作用。第二种药物由Notch-1反义寡核苷酸组成，显示在体外诱导几种人类肿瘤细胞类型的凋亡。这两种药物的组合，第一种具有抗转移和抗增殖特性，第二种诱导凋亡，可以在体内互补以控制裸鼠中肿瘤细胞的生长，并为进一步的研究铺平道路。拟定商业应用：本提案中描述的实验数据将为启动用于不可切除NSCLC辅助治疗的新型联合药物的临床开发提供概念证明。这些是美国和世界上最常见的恶性肿瘤之一，采用当前标准的化疗和放疗治疗预后不良。NSCLC本身就是一个主要的制药市场。而且，这些产品的应用可能会扩展到结肠癌、宫颈癌等恶性肿瘤，进一步增加这项工作可能的商业应用。

The purpose of the proposed study is to evaluate the effectiveness of two potential anti-tumor agents, both separately and in combination, in an adoptive transfer model of lung cancer. The first agent is recombinant human CC10, which has recently been shown to have anti-metastatic and tumor suppressive effects on a variety of human tumor cell types in vitro. The second agent consists of a Notch-1 anti-sense oligonucleotide, shown to induce apoptosis in several human tumor cell types in vitro. The combination of these two agents, the first having anti-metastatic and anti- proliferative properties, and the second inducing apoptosis, may complement each other in vivo to control the growth of tumor cells in nude mice and pave the way for further studies. PROPOSED COMMERCIAL APPLICATION: Data from the experiments described in this proposal would provide proof of concept to initiate the clinical development of novel combination agents for the adjuvant treatment of unresectable NSCLC. These are among the most common malignancies in the US and the world, and carry a dismal prognosis with the current standard of care chemo- and radiation therapy. In itself, NSCLC represents a major pharmaceutical market. Moreover, the applications of these products may be extended to colon cancer, cervical cancer and other malignancies, further increasing the possible commercial applications of this work.