RECOMBINANT HUMAN CC10 AND NOTCH-1 ANTAGONIST IN NSCLC

本研究的目的是评估两种潜在的抗肿瘤药物单独使用和联合使用在肺癌过继转移模型中的有效性。第一种药物是重组人CC10，它最近在体外被证明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，在体外诱导几种人类肿瘤细胞类型的凋亡。这两种药物联合使用，前者具有抗转移和抗增殖的特性，后者具有诱导细胞凋亡的特性，可能在体内相互补充，控制裸鼠肿瘤细胞的生长，为进一步的研究铺平道路。拟议的商业应用：本提案中描述的实验数据将为启动不可切除的非小细胞肺癌辅助治疗的新型联合药物的临床开发提供概念证明。这是美国和世界上最常见的恶性肿瘤之一，按照目前的化疗和放疗标准，预后很差。就其本身而言，NSCLC代表了一个主要的医药市场。此外，这些产品的应用可能会扩展到结肠癌、宫颈癌等恶性肿瘤，进一步增加了本工作的商业应用可能性。

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.