ANTI-ANDROGEN RECEPTOR MABS FOR HUMAN PROSTATE CANCER

用于人类前列腺癌的抗雄激素受体 MABS

• 批准号: 3493269
• 负责人: CHARLES C-Y SHIH
• 金额: $ 5万
• 依托单位: PHARMINGEN
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-04-01 至 1993-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3493269
• 关键词: Baculoviridae; DNA binding protein; androgen receptor; antigen antibody reaction; antigens; antitumor antibody; biomarker; epitope mapping; hormone binding protein; immunoprecipitation; insect virus; laboratory mouse; male; method development; monoclonal antibody; neoplasm /cancer immunodiagnosis; prostate neoplasms; tissue /cell culture; transfection /expression vector

Each year more than one hundred thousand cases of prostate cancer have been diagnosed in the United States and which is the first in solid tumor incidence and second in cancer related death in the American male population. Yet, the factors which are involved in prostate carcinogenesis, except for the presence of androgen, remain unclear. Recently, scientists have studied oncogene amplification and tumor suppressor gene expression in prostate tissue and failed to establish a relationship between the expression of these genes and prostate carcinogenesis. On the other hand, it has been shown that metastatic prostate cancer patients with higher pretreatment plasma testosterone levels tend to have a greater survival rate when receiving primary hormonal therapy than those patients with low testosterone levels at the time of diagnosis. Thus, the androgen and androgen receptor (AR) expression may play an important role during prostate carcinogenesis. Recently, the anti-AR monoclonal antibody (Mab) has become available which make the assessment of AR levels and their localization in tissues possible. However, these anti-AR Mabs were developed using merely peptide fragments as immunogens. Consequently, these Mabs do not always stain tissue effectively and do not react with AR functional domains. Thus, the application of these Mabs has been limited. In addition, the lack of high affinity anti-Ar mabs and purified human AR proteins has hampered the development of a convenient ELISA test for clinical applications. In this proposal we will focus on the production and purification of full-length AR proteins from insect cells infected with baculovirus vector carrying the AR gene; these proteins will be used as immunogens to produce high affinity anti-AR Mabs and develop immunoassays for the clinical applications in prostate cancer.

每年有超过十万例前列腺癌患有 在美国被诊断出，这是实体瘤 美国男性的发病率，第二次与癌症有关的死亡 人口。 但是，前列腺涉及的因素 除了存在雄激素外，癌变尚不清楚。 最近，科学家研究了癌基因扩增和肿瘤 抑制前列腺组织中的基因表达，未能建立 这些基因和前列腺的表达之间的关系 致癌作用。 另一方面，已经表明转移 预处理血浆睾丸激素的前列腺癌患者 接收初级时，水平的存活率往往更高 激素治疗比那些在睾丸激素水平低的患者 诊断时间。 因此，雄激素和雄激素受体（AR） 表达可能在前列腺癌发生过程中起重要作用。 最近，抗AR单克隆抗体（MAB）已获得 这使评估AR水平及其在组织中的定位 可能的。 但是，这些反AR mab仅使用 肽片段作为免疫原子。 因此，这些mab并不总是 有效的污渍组织，不与AR功能结构域反应。 因此，这些mAb的应用受到限制。 另外， 缺乏高亲和力抗AR mAb和纯化的人类AR蛋白具有 阻碍了方便的ELISA测试进行临床的开发 申请。 在此提案中，我们将专注于生产和 从感染的昆虫细胞中纯化全长AR蛋白 带有AR基因的杆状病毒载体；这些蛋白质将用作 免疫原子可产生高亲和力抗Ar-Ar-Ar-Ar-Ar-Ar-Ar-Armabs并产生免疫测定 用于前列腺癌中的临床应用。