Gene and Virus Therapy Shared Resource

基因和病毒治疗共享资源项目摘要 马约诊所长期致力于转化有前景的癌症疗法，使患者受益 到临床实践。新药的转化，包括有前途的基于病毒的疗法，从周期 从基础和临床前研究到临床试验，需要专业知识和设施，这在学术界是不常见的。 设置.因此，临床试验过程的启动可能会显著延迟或完全受阻， 学术研究者/临床医生。学术界可以采取的途径很少， 研究人员/临床医生试图获得必要的专业知识和设施。马约诊所 分子医学系（DMM）在现场建立了必要的核心资源来翻译病毒- 从马约诊所的基础研究到I期和II期临床试验。马约诊所癌症中心（MCCC） 该资源的组成部分，基因和病毒治疗共享资源（GVTSR），是在 与MCCC基因和病毒治疗计划相结合，为MCCC成员提供最广泛的 灵活地访问翻译基于病毒的 以有效和具有成本效益的方式将治疗转化为临床试验。GVTSR开发了资源 和专业知识，以生产大规模的临床级病毒产品，进行毒理学和 动物模型中病毒治疗剂的药理学表征，并确保这些药物的质量。 活动GVTSR的标志性设施是2000平方米。英尺病毒载体生产的生产设施 实验室，有一个GMP套件，能够高达75 L的病毒生产运行，和一个临床前套件，用于大型 大规模病毒生产工艺开发。额外的实验室空间专用于Tox/Pharm实验室 以及马约诊所综合动物设施的可用性，以支持GVTSR 需求这些GVTSR活动必须使用联邦强制规范（药物非临床研究质量管理规范）进行 和药品生产质量管理规范），需要特定的人员培训、设施和质量控制， 质量保证计划。GVTSR还与FDA建立了牢固的关系， 联邦对这些活动的权力。GVTSR可提供IND的2种主要组件 应用：产品制造和安全性测试的描述，以及毒理学和 在适当的动物模型中对产品进行药理学表征。同样重要的是， GVTSR开发大规模病毒生产和纯化工艺的能力， 临床前研究以及临床级产品的生产。GVTSR密切合作， 在临床试验方案的开发和监管批准中与临床医生合作。这一全面 这种方法已经导致MCCC成员将多种基于病毒的新疗法转化为13个I期和2期 II期临床试验，治疗15种不同类型的肿瘤。

GENE AND VIRUS THERAPY SHARED RESOURCE PROJECT SUMMARY Mayo Clinic has a long-standing commitment to translating promising cancer therapies that benefit its patients to its clinical practice. The translation of new drugs, including promising virus-based therapies, from the cycles of basic and preclinical research to clinical trials requires expertise and facilities not often found in an academic setting. Thus, the initiation of the clinical trial process can be significantly delayed or completely blocked for the academic researcher/clinician. There are very few avenues that can be taken by the academic researcher/clinician to try and gain access to the necessary expertise and facilities. The Mayo Clinic Department of Molecular Medicine (DMM) established the necessary core resources on-site to translate virus- based research at the Mayo Clinic to Phase I and II clinical trials. The Mayo Clinic Cancer Center (MCCC) component of this resource, the Gene and Viral Therapy Shared Resource (GVTSR), was developed in conjunction with the MCCC Gene and Virus Therapy Program and provides MCCC members the broadest flexibility to access the complete range of expertise and services required for translation of a virus-based therapy to a clinical trial in an efficient and cost-effective manner. The GVTSR has developed the resources and expertise to manufacture large-scale clinical grade viral products, to conduct toxicological and pharmacological characterization of viral therapeutics in animal models, and to assure the quality of these activities. The GVTSR signature facility is the 2000 sq. ft. manufacturing facility of the Viral Vector Production Laboratory, with one GMP suite capable of up to 75 L virus production runs, and a preclinical suite for large- scale virus production process development. Additional laboratory space is dedicated to the Tox/Pharm Lab and QC functions, as well the availability of Mayo Clinic comprehensive animal facilities to support GVTSR needs. These GVTSR activities must be done using federally mandated practices (Good Laboratory Practices and Good Manufacturing Practices) that require specific personnel training, facilities, and quality control and quality assurance programs. The GVTSR has also developed a strong relationship with the FDA who has federal authority over these activities. The GVTSR can supply 2 of the major components of an IND application: the descriptions of the product manufacturing and safety testing, and the toxicology and pharmacology characterization of the product in appropriate animal models. Of equal importance are the capabilities of the GVTSR to develop large-scale viral production and purification processes to support preclinical studies as well as the manufacture of clinical grade product. The GVTSR works in close partnership with a clinician in the development and regulatory approval of a clinical trial protocol. This comprehensive approach has resulted in MCCC members translating multiple novel virus-based therapies to 13 Phase I and 2 Phase II clinical trials to treat 15 different tumor types.