NOVEL THERAPY FOR CANDIDA ALBICANS INFECTION

白色念珠菌感染的新疗法

• 批准号: 2792881
• 负责人: JAMES W LARRICK
• 金额: $ 9.32万
• 依托单位: PANORAMA RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2792881
• 关键词: Candida albicans; affinity chromatography; antiidiotype antibody; biotechnology; candidiasis; genetically modified plants; immunological substance; immunotherapy; mucosal immunity; plant extracts; protein purification; technology /technique development; toxin; western blottings

Severe mucosal Candida albicans is a major cause of morbidity and mortality in immunosuppressed individuals and less toxic therapeutic agents are needed. Our collaborator, Dr. Luciano Polonelli has prepared a number of yeast killer toxin (KT) anti-idiotype antibodies (KT-ID Mab) that mimic the cytotoxic activity versus Candida and Pneumocystis of the native killer toxin. Native KT Cannot be used because it is unstable, immunogenic and has much reduced activity at neutral pH. The KT-ID Mab applied topically in rodent models was effective versus both vaginal candidiasis and pulmonary P. carinii infections. The plant molecular biology unit of Panorama Research Inc. (PRI) has pioneered proprietary methods for the production of secretory lgA antibodies in transgenic plants. SigA plantibodies are the preferred form of antibody therapy for mucosal use. The overall goal of the present project is to prepare an SIgA form of this anti-ID as an economical, stable, therapeutic for C. albicans infection. In phase I we will construct secretory IgA plantibody expression cassettes using the bioactive scFv having demonstrated candidacidal activity. These will be used to transform tobacco by particle bombardment and plants expressing assembled SIgA will be selected. Next we will demonstrate cytotoxic activity of the purified anti-ID SIgA plantibody using in vitro candidacidal assays. Successful completion of this project will demonstrate a general proprietary method to combat difficult mucosal pathogens. PROPOSED COMMERCIAL APPLICATIONS: Severe mucosal candidiasis infections are a major problem. A novel therapeutic represents a significant market opportunity.

严重的粘膜白色念珠菌是免疫抑制个体发病和死亡的主要原因，需要毒性较小的治疗剂。我们的合作者Luciano Polonelli博士制备了许多酵母杀伤毒素（KT）抗独特型抗体（KT-ID Mab），模拟天然杀伤毒素对念珠菌和肺孢子虫的细胞毒性活性。不能使用天然KT，因为它不稳定，具有免疫原性，并且在中性pH下活性大大降低。在啮齿动物模型中局部应用的KT-1D Mab对阴道念珠菌病和肺部卡氏肺孢子虫感染均有效。全景研究公司的植物分子生物学部门。(PRI)开创了在转基因植物中生产分泌型IgA抗体的专有方法。 SigA植物抗体是用于粘膜用途的抗体疗法的优选形式。本项目的总体目标是制备这种抗ID的SIgA形式，作为治疗C.白色念珠菌感染 在第一阶段，我们将构建分泌型伊加plantibody表达盒使用的生物活性的单链抗体已证明杀念珠菌活性。这些将用于通过粒子轰击转化烟草，并选择表达组装的SIgA的植物。接下来，我们将使用体外杀念珠菌测定来证明纯化的抗ID SIgA植物抗体的细胞毒性活性。该项目的成功完成将证明一种通用的专有方法，以打击困难的粘膜病原体。拟议的商业应用：严重的粘膜念珠菌感染是一个主要问题。一种新的治疗方法代表了一个重要的市场机会。