Pathway to Accelerate Clinical Development in Gene Transfer: cGMP Vector Core

描述（由申请人提供）：此申请详细介绍了费城儿童医院（CHOP）临床病媒核心设施的扩展和升级。我们建议建设一个新的生产套件，同时对现有的cGMP生产套件进行翻新，以满足对载体的日益增长的需求，以支持基因治疗的转化研究。这种扩展的双制造套件配置将提供互补的操作功能，增强的容量和灵活性，以及有效支持从临床前研究到新产品许可的临床转化研究的所有阶段所需的能力。CHOP的载体核心项目直接支持转化医学研究，以实现人类基因组计划的全部潜力。基于基因的疗法已经进行了近二十年的临床试验，但直到现在才达到临床试验显示疗效的程度，这一点在过去一年的《新英格兰医学杂志》上得到了证明（Maguire et al (2008) N Engl J Med 358:2240）；Aiuti et al .（2009）中华医学杂志（英文版）360:518。这些研究表明，基因疗法对一种先天性失明和一种严重的联合免疫缺陷疾病的安全性和有效性。这类新型疗法在治疗许多其他遗传疾病方面具有巨大潜力，但前提是能够建立响应性和生产性载体核心基础设施，以支持有希望的早期研究。对于新型治疗药物的开发，最好的成功之路往往是从临床前数据最可靠的产品开始，即使市场很小。像CHOP这样的学术机构与NIH合作，能够按照行业标准生产载体，但不受市场压力的影响。临床级载体的可用性对于基因治疗的临床试验至关重要。高质量的病媒在商业领域是不容易获得的——因此，该设施使美国国立卫生研究院资助的研究人员能够使用。现有的AAV研究人员在大型动物模型中取得了强有力的结果，加上已经在进行的临床试验中有明确的疗效证据，这表明该领域的研究步伐将大大加快。

DESCRIPTION (provided by applicant): This application details the expansion and upgrade of a Clinical Vector Core facility at The Children's Hospital of Philadelphia (CHOP). We are proposing the construction of a new manufacturing suite and the simultaneous renovation of an existing cGMP manufacturing suite to meet the growing demand for vector to support translational research in gene therapy. This expanded, dual manufacturing suite configuration will provide complementary operational functions, enhanced capacity and flexibility, and needed capability to efficiently support all stages of clinical translational research, from pre-clinical studies to new product licensure. CHOP's vector core project directly supports translational medicine research seeking to realize the full potential of the Human Genome Project. Gene-based therapies have been in clinical trials for nearly two decades, but are only now reaching the point where clinical trials are showing efficacy, as evidenced by publications in the New England Journal of Medicine over the past year (Maguire et al (2008) N Engl J Med 358:2240); Aiuti et al (2009) N Engl J Med 360:518). These studies have shown gene therapy's safety and efficacy for a form of congenital blindness and a form of severe combined immunodeficiency disorder. This novel class of therapeutics has great potential for the treatment of many other genetic diseases, but only if responsive and productive vector core infrastructures can be built in support of promising early research. For the development of novel classes of therapeutics, the best route to success is often to start with products where the pre-clinical data are most robust, even if the market is small. Academic facilities such as CHOP's, in partnership with NIH, are able to manufacture vector at industry-level standards, but are not subject to the pressures of the marketplace. The availability of clinical-grade vectors is absolutely critical for clinical trials in gene therapy. High-quality vector is simply not readily available in the commercial sector - as such, this facility is enabling NIH-funded investigators. The strong pipeline represented by existing AAV Investigators with robust results in large animal models, coupled with clear evidence of efficacy in clinical trials already underway (vide supra), suggests that the pace of research in the field will accelerate considerably.