Gene and Virus Therapy Shared Resource

An Academic Team That Translates Virus-Based Therapy Products To Phase I/II Clinical Trials

Mark J. Federspiel, Ph.D.
Director

The Gene and Virus Therapy Shared Resource (GVTSR) fills a critical need to facilitate the translation of promising virus-based therapies emerging from the basic bench investigations of Mayo Clinic Cancer Center investigators as they move into preclinical and clinical trials. The Shared Resource meets all the rigorous requirements of the U.S. Food and Drug Administration (FDA) for Phase I/II clinical trials, including the ability to provide adequate clinical grade material to determine the efficacy, toxicological and pharmacological characterization of the candidate agent as well as expertise with all steps of the regulatory process.

Translation of new drugs, biologics or medical devices from the cycles of research to clinical trials requires the conversion of data, procedures and product from research-grade to medical-grade appropriate for use in humans. Many of these activities must be done using federally-mandated procedures and practices including Good Manufacturing Practices (GMP) that require specific personnel training and expertise, unique facilities and equipment, and robust quality assurance programs.

Gene Therapy Developmental Process - Cycles of preclinical research testing the efficacy of different viral vectors in vitro and in animal models accumulates the data that justifies the testing of the concept in human clinical trials. The transition from laboratory based experimental procedures to human clinical trials requires capabilities to characterize the therapeutic, to manufacture a clinical grade product using Good Manufacturing Practices (GMP), and to have these services integrated with the clinical trial protocol that will use the product. All of these procedures and results are reviewed by the FDA, the Recombinant DNA Advisory Committee (RAC), and institutional committees [Institutional Review Board (IRB) and Institutional Biosafety Committee (IBC)].

To meet these needs, the Gene and Virus Therapy Shared Resource has three components, the Viral Vector Production laboratory (VVPL), the Viral Toxicology Pharmacology Laboratory (VTPL) and Quality Assurance (QA). All three of these units work in collaboration with each principal investigator to determine what services are necessary for each unique project, to perform these services, and to document the protocols and results.

The Viral Vector Production Laboratory performs services required for the large-scale process development and the manufacture of the viral product for human use.

The Viral Toxicology Pharmacology Laboratory performs services required for characterizing the toxicological and pharmacological effects of the viral product in animal models required by the FDA.

The third component of the GVTSR, Quality Assurance, is in charge of the monitoring and oversight of all GVTSR GMP and QC activities. The Quality Assurance Officer, who is independent of the VVPL and VTPL operations, directs the QA unit and has the authority to determine if a clinical product manufactured by the VVPL meets the release specifications for clinical use, and provides audits of the Tox/Pharm preclinical studies.

In addition to supporting ongoing research for a number of Cancer Center Programs, the Gene and Virus Therapy Shared Resource has made possible a number of clinical trials, including:

• Trial of Intraperitoneal Administration of a CEA-Expressing Derivative Manufactured from a Genetically Engineered Strain of Measles Virus in Patients with Recurrent Ovarian Cancer
• Phase I Trial of a Measles Virus Derivative Producing CEA (MV-CEA) in Patients With Recurrent Glioblastoma Multiforme
• Phase I Trial of Systemic Administration of Edmonston Strain of Measles Virus, Genetically Engineered to Express NIS, With or Without Cyclophosphamide, in Patients With Recurrent or Refractory Multiple Myeloma

Organizational Chart