Treatment of non-small cell lung cancer with a CCL14 monoclonal antibody

描述(申请人提供)：肺癌是世界上最常见的癌症，也是美国癌症死亡最多的原因。现有的治疗方法包括手术、放射或化疗来杀死肿瘤细胞，但这些选择对绝大多数患者来说是不够的。因此，有必要开发新的治疗方法。最有前途的发展领域之一是免疫疗法，它对免疫系统进行重新编程，以识别和消除肿瘤。我们确定了一种表达在肺癌细胞上的蛋白质，它可能通过调节宿主免疫细胞的招募来允许肿瘤逃避免疫系统。我们的目标是开发一种中和抗体，可以抑制这种蛋白的活性，重新激活抗肿瘤免疫反应，导致肿瘤消退。我们已经生产出了针对这个靶点的单抗。这项建议的第一个目标是在分子和细胞分析中表征抗体，以根据结合靶标和抑制其信号活性来选择最佳抗体。该提案的第二个目的是在小鼠肿瘤模型中测试该抗体，并确定该抗体是否抑制肿瘤生长。这一提议是开发用于人类治疗的抗体的基础。如果成功，它将带来一种新的治疗选择，将提高肺癌患者的存活率。

DESCRIPTION (provided by applicant): Lung cancer is the most prevalent cancer worldwide and responsible for the most cancer deaths in the United States. Existing therapies include surgery, radiation, or chemotherapy to kill the tumor cells, but these options are not adequate for the vast majority of patients. Thus, there is a significant need to develop new therapeutic approaches. One of the most promising areas of development is immunotherapy, which reprograms the immune system to recognize and eliminate the tumor. We identified a protein that is expressed on lung cancer cells that may allow a tumor to evade the immune system by regulating the recruitment of host immune cells. Our goal is to develop a neutralizing antibody that will inhibit the activity of this protein and reactivate the anti- tumor immune response, resulting in tumor regression. We have produced monoclonal antibodies against this target. This first aim of this proposal is to characterize the antibodies in molecular and cellular assays to select the optimal antibody based upon binding the target and inhibiting its signaling activity. The second aim of the proposal will test the antibody in mouse tumor models and determine if the antibody inhibits tumor growth. This proposal is the foundation for development of an antibody for use as human therapeutics. If successful, it will result in a new treatment option tha will improve survival for patients with lung cancer.