Chimeric CD80-SA as a Novel Cancer Vaccine
嵌合 CD80-SA 作为新型癌症疫苗
基本信息
- 批准号:7126430
- 负责人:
- 金额:$ 41.74万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-09-27 至 2007-08-31
- 项目状态:已结题
- 来源:
- 关键词:B cell lymphomaCD28 moleculeT lymphocyteaffinity chromatographybinding proteinsbiotechnologybiotincell linecell surface receptorschimeric proteinsdisease /disorder modeldrug adverse effectglycoproteinslaboratory mouseleukocyte activation /transformationlung neoplasmsneoplasm /cancer immunotherapyneoplasm /cancer vaccinenonhuman therapy evaluationprotein engineeringprotein purificationvaccine developmentvaccine evaluation
项目摘要
DESCRIPTION (provided by applicant): Cancer is one of the major causes of death in the U.S. and many developed countries with an estimated economic burden of over 100 billion dollars in direct and indirect costs in the U.S. alone. Although surgery, chemotherapy, and radiotherapy are commonly used treatment modalities, these therapies not only fail to effectively manage cancer, but also are associated with adverse side effects due to their lack of specificity against cancer cells. Therefore, there is an acute need for the development of more effective and tumor-specific therapies for the treatment and prevention of cancer.
Immunotherapy has recently gained impetus as a cancer treatment modality due to its specificity, safety, and its ability to generate immunological memory that can safeguard against recurrences. Tumor cells genetically modified to express costimulatory molecules, such as CD80, have been shown to be effective in preventing tumor development and eradicating existing tumors when used as a vaccine in preclinical studies. This approach has been the subject of several recent Phase l/ll clinical trials with encouraging results. However, the expression of costimulatory molecules via gene therapy is elaborate, inefficient, expensive, and associated with several safety concerns. To circumvent these problems, Apolmmune, Inc., is developing vaccines based on a novel proprietary technology, designated as ProtEx(tm), that allows for the display of exogenous proteins on the surface of tumor cells in a rapid (<2 hrs) and efficient (100% of the targeted cells) manner without the costs or safety issues inherent to gene therapy. ProtEx involves the generation of chimeric proteins with core streptavidin, biotinylation of the cell surface, and decoration with chimeric proteins. Most importantly, since the chimeric proteins exist as oligomers they can effectively crosslink their counter receptors on relevant immune cells for the delivery of potent signals, thereby generating effective anti-cancer immune responses. Proof-of-principle for a proprietary vaccine (ApoVax(tm)) based on the use of tumor cells decorated" with a chimeric human CD80 molecule (CD80-SA) has been generated in a preclinical tumor model and ex vivo clinical studies. This application is intended to support the development of ApoVax(tm)as a lead vaccine product that will eventually be used in Phase I clinical trials, which will be the subject of a Phase II SBIR application. It specifically focuses on i) high yield production, purification, and characterization of the CD80-SA protein, ii) developing a final stable formulation for the protein and ApoVax(tm) vaccine, iii) determining the most effective treatment regimens in preclinical studies, vi) performing toxicological studies, and v) producing pilot cancer vaccine materials under current GMP conditons. The long term success of this project may allow for the development of ApoVax(tm) as a multi-million dollar cancer vaccine product and improvement in the longevity and quality of life for millions of cancer patients.
描述(由申请人提供):癌症是美国和许多发达国家的主要死亡原因之一,仅在美国,直接和间接成本的经济负担估计超过1000亿美元。虽然手术、化疗和放疗是常用的治疗方式,但这些疗法不仅不能有效地控制癌症,而且由于缺乏针对癌细胞的特异性而与不良副作用相关。因此,迫切需要开发用于治疗和预防癌症的更有效和肿瘤特异性的疗法。
免疫疗法由于其特异性、安全性和产生免疫记忆的能力而成为癌症治疗的一种方式。经遗传修饰以表达共刺激分子(如CD 80)的肿瘤细胞已被证明在临床前研究中用作疫苗时可有效预防肿瘤发展并根除现有肿瘤。这种方法已经成为最近几个I/II期临床试验的主题,具有令人鼓舞的结果。然而,通过基因疗法表达共刺激分子是复杂的、低效的、昂贵的,并且与若干安全性问题相关。为了避免这些问题,Apolmmune,Inc.,该公司正在开发基于一种新的专有技术的疫苗,称为ProtEx(tm),该技术允许以快速(<2小时)和有效(100%的靶细胞)的方式在肿瘤细胞表面展示外源蛋白,而没有基因治疗固有的成本或安全问题。ProtEx涉及产生具有核心链霉亲和素的嵌合蛋白,细胞表面的生物素化,以及用嵌合蛋白修饰。最重要的是,由于嵌合蛋白作为寡聚体存在,它们可以有效地交联相关免疫细胞上的反受体,以传递有效的信号,从而产生有效的抗癌免疫应答。在临床前肿瘤模型和离体临床研究中,已经产生了基于使用嵌合人CD 80分子(CD 80-SA)修饰的肿瘤细胞的专有疫苗(ApoVax(tm))的原理证明。该申请旨在支持ApoVax(TM)作为主要疫苗产品的开发,该产品最终将用于I期临床试验,这将是II期SBIR申请的主题。它特别关注i)CD 80-SA蛋白的高产率生产、纯化和表征,ii)开发蛋白和ApoVax(tm)疫苗的最终稳定制剂,iii)确定临床前研究中最有效的治疗方案,vi)进行毒理学研究,以及v)在当前GMP条件下生产中试癌症疫苗材料。该项目的长期成功可能会使ApoVax(tm)成为一种价值数百万美元的癌症疫苗产品,并改善数百万癌症患者的寿命和生活质量。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ROLF M HUSEBY其他文献
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{{ truncateString('ROLF M HUSEBY', 18)}}的其他基金
ApoFasL: a Novel Immunotherapeutic for T1D
ApoFasL:一种新型 T1D 免疫疗法
- 批准号:
7325628 - 财政年份:2007
- 资助金额:
$ 41.74万 - 项目类别:
Chimeric CD80-SA as a Novel Cancer Vaccine
嵌合 CD80-SA 作为新型癌症疫苗
- 批准号:
6992408 - 财政年份:2005
- 资助金额:
$ 41.74万 - 项目类别: