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

描述(由申请人提供)：本申请详细说明了费城儿童医院(CHOP)临床病媒核心设施的扩建和升级。我们建议建造一个新的生产套件，同时更新现有的cGMP生产套件，以满足对载体的日益增长的需求，以支持基因治疗中的翻译研究。这种扩展的双制造套件配置将提供互补的运营功能、增强的能力和灵活性，以及有效支持从临床前研究到新产品许可的所有临床转化研究阶段所需的能力。CHOP的载体核心项目直接支持寻求实现人类基因组计划全部潜力的转化医学研究。基于基因的疗法已经在临床试验中进行了近20年，但过去一年发表在《新英格兰医学杂志》(Maguire等人(2008)N Engl J Med 358：2240；Aiuti等人(2009)N Engl J Med 360：518)上的文章证明了临床试验显示了有效性。这些研究表明，基因疗法对一种形式的先天性失明和一种严重的联合免疫缺陷疾病是安全和有效的。这类新的疗法在治疗许多其他遗传疾病方面具有巨大的潜力，但前提是能够建立反应灵敏和富有成效的载体核心基础设施，以支持有希望的早期研究。对于新型疗法的开发，最好的成功途径往往是从临床前数据最稳健的产品开始，即使市场很小。像CHOP‘s这样的学术机构与NIH合作，能够以行业标准制造载体，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是绝对关键的。高质量的病媒在商业部门并不容易获得--因此，这一设施使NIH资助的调查人员能够获得。现有的AAV研究人员代表着强大的渠道，在大型动物模型中取得了强劲的结果，再加上已经在进行的临床试验中的有效性的明确证据(见上文)，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.