Agri-Pharmaceutical Cancer Therapeutics

现代基因组学和蛋白质组学的发展为以合理多肽为基础的癌症治疗方法的发展创造了机会。使用植物生物质生产系统，现在有可能以相当低的成本和大量生产治疗性多肽和蛋白质。这项提议的总体目标是开发基于多肽的癌症疗法，这种疗法可以从植物生物质，特别是烟草中产生。在与大规模生物学公司的合作下，詹姆斯·格雷厄姆·布朗癌症中心的科学家们已经开发出在烟草植物中表达多肽和蛋白质的能力。位于肯塔基州欧文斯伯勒的大型生物加工厂具有生产以烟草为基础的疗法的GMP的能力。这项提案将利用布朗癌症中心在抗癌药物和疫苗开发方面的专业知识以及在植物分子生物学和表达技术方面的大规模生物学专业知识来实现以下具体目标： 1.鉴定针对癌细胞表面表达的两种细胞蛋白核仁素和α-烯醇酶的生长抑制肽适配子。 2.开发可在烟草中生产的有效人乳头瘤病毒疫苗。 米勒博士在适配子开发方面的独特和互补的经验，以及简森博士在疫苗研制方面的经验，将确保该项目的成功。这些目标的实现将给肯塔基州带来双重优势，即开发具有治疗潜力的新化合物，并为参与该计划的农民创造收入。在该州发展可行的农用制药行业将带来额外的好处。这项拨款中提出的实验将允许布朗癌症中心的科学家将他们的实验室观察转化为早期临床试验。

The development of modern genomics and proteomics has created an opportunity for the development of rational peptide-based cancer therapeutics. Using plant-biomass production systems, it is now possible to generate therapeutic peptides and proteins quite inexpensively and in large quantities. The overall goal of this proposal is to develop peptide-based cancer therapeutics which can be produced by plant biomass, particularly tobacco. In collaboration with Large Scale Biology, Inc., scientists at the James Graham Brown Cancer Center have developed the ability to express peptides and proteins in tobacco plants. The Large Scale Biology processing plant at Owensboro, Kentucky has the capability of GMP production of tobacco-based therapeutics. This proposal will take advantage of the Brown Cancer Center expertise in cancer drug and vaccine development and the Large Scale Biology expertise in plant molecular biology and expression technology to accomplish the following specific aims: 1. To identify growth inhibitory peptide aptamers targeted to nucleolin and alpha-enolase, two cellular proteins expressed on the surface of cancer cells. 2. To develop effective human papillomavirus vaccines that can be produced in tobacco. The unique and complementary experience of Dr. Miller in aptamer development and Dr. Jenson in vaccine creation will ensure the success of this project. The accomplishment of these goals will have the duel advantage for Kentucky of developing new compounds with therapeutic potential and generating revenue for farmers who participate in the program. The development of a viable agripharmaceutical industry in the state will have additional benefits. The experiments which are proposed in this grant will allow Brown Cancer Center scientists to translate their laboratory observations into early phase clinical trials.