Development of a New Antiangiogenic Tumor Blocker SBD 1

抑制肿瘤血管生成（新生血管向肿瘤组织生长）是一种新的抗癌治疗方法。到目前为止，几种血管生成抑制剂完成的I/II期临床试验结果验证了肿瘤血管生成作为抗癌治疗有效靶点的概念。然而，同样的研究强调需要新的、更有效的血管生成抑制剂。为了满足这一需求，我们从人尿中分离出一种新的蛋白（SBD.1），该蛋白在体外特异性阻断毛细血管内皮细胞的增殖（ID50=15NG/ML），在绒毛膜促生实验中阻断血管生成，并在体内阻断两种生长（Lewis肺癌，T/C=0.04, 20um /kg/day），使SBD.1成为已知最有效的血管生成抑制剂之一。SBD/1的测序结果表明，它是一种新蛋白，其轻微的蛋白水解导致产生更小的肽而不失去抑制活性。在此，我们提出a)在重组系统中克隆和表达SBD.1；b)分离SBD.1活性片段并测序；c)将纯化的SBD.1在人前列腺癌、肺癌和乳腺癌异种移植物上进行裸鼠实验，进一步评估其抗肿瘤活性。该项目将克隆出一种新的治疗活性蛋白，该蛋白可能是人血管和肿瘤发生的重要内源性调节因子。拟议的商业应用：SBD.1的开发满足了制药行业对一种新的、更好的血管生成抑制剂的迫切需求。SBD.1目前主要用于抗癌治疗，以后可能会扩展到血管病变的治疗，如黄斑变性和某些心血管疾病。同时，SBD.1也可以作为实验室血管生成研究的试剂进行商业化。综上所述，这些应用代表了sbd的巨大潜在市场

Inhibition of tumor angiogenesis-the growth of new blood vessels towards the tumor mass-is a new and promising approach to anti-cancer therapy. The results of Phase I/II clinical trials completed so far with several angiogenesis inhibitors validate the concept of tumor angiogenesis as effective target for anti-cancer therapy. However, the same studies stress the need for novel, more potent angiogenesis inhibitors. We addressed this need by isolating the human urine a new protein (SBD.1), which specifically blocks the proliferation of capillary endothelial cells in vitro (ID50=15NG/ML), angiogenesis in chorioallentoic membrane assay, and two growth in vivo (Lewis Lung Carcinoma, T/C=0.04 at 20umum/kg/day), placing SBD.1 among the most potent known angiogenesis inhibitors. Sequencing of SBD/1 showed it is a novel protein and its mild proteolysis resulted in the generation of smaller peptides without losing the inhibitory activity. Here, we propose to a) clone and express SBD.1 in a recombinant system; b) isolate and sequence the activity SBD.1 fragments; c) test the purified SBD.1 on prostate, lung and breast carcinoma human xenografts in nude mice to further assess its anti-tumor activity This project will result in the cloning of a novel therapeutically-active protein, which may be an important endogenous regulator of angio- and tumorigenesis in humans. PROPOSED COMMERCIAL APPLICATIONS: The development of SBD.1 addresses a pressing need in the pharmaceutical industry for a new, better angiogenesis inhibitor. Currently targeting anti-cancer therapy, the use of SBD.1 might be later extended to the treatment of vascular pathologies, such as macular degeneration and certain cardiovascular diseases. Meanwhile, SBD.1 can also be commercialized as reagent for laboratory research on angiogenesis. Taken together, these applications represent a substantial potential market for SBD.1