Work packages

Research & Development
for Advanced Therapies

The overall objective of ARDAT is to develop and provide the data and tools to fill gaps in our knowledge-base in the areas of immunology and metabolism of viral gene/cell therapy to accelerate the research and development of Advanced Therapy Medicinal Products. This will involve the development of data and tools for gene and cell therapy, to provide developers and regulators with the information they need to more swiftly move these potentially transformative medicines forward and to patients in need.

Work package 1

Project Coordination/Management

  • Provide scientific coordination and management of the program to ensure efficient and within budget successful achievement of objectives, completion of deliverables and milestones.
  • Ensure that ARDAT is carried out under EU regulations, according to the contractual legal requirements and the Good Practice as stated in the Financial Guidelines.
  • Ensure a platform is in place to facilitate the data sharing and communication process within ARDAT
  • Establish and implement a strategy to promote dissemination and exploitation of ARDAT scientific results
  • Ensure sustainability of model systems, databases, and biobanking generated during ARDAT activities

Work package 2

Develop better, standardized models for predicting product immunogenicity in humans

  • Utilize three mouse disease models to investigate the impact of immunity on ATMPs
  • Develop 3D organoid models to investigate immune mechanisms that affect AAV transduction efficiency and toxicity of target cells
  • Characterize the local and systemic immune reactions to AAV or cell therapy delivered through different administration routes
  • Establish immune phenotyping and genotyping methods
  • Understand the impact of the innate immune system, including complement and non-professional antigen-presenting cells, on the initiation of the immune response to ATMPs

Work package 3

Molecular stability and metabolism of AAV

  • Assess the effect of vector genome dilution, as a consequence of target tissue growth
  • Define metabolism of the therapeutic vector genome in different cell types to understand whether rates of degradation, episomal maintenance, or integration, and metabolic stress induced by AAV vector transgene expression vary from cell to cell
  • Mitigate the loss of vector genomes and explore the idea of stabilizing AAV vector genomes within the target cell and explore strategies to improve the persistence of vector genomes
  • Generate hybrid vectors to accommodate transgenes that exceed the packaging capacity of AAV or nonviral counterparts and have a higher efficiency of concatemerisation, and full-length vector genome reconstitution
  • Validate the newly generated hybrid vectors/capsids in disease animal models

Work package 4

Understand the clinical factors around pre-existing immunity limiting patient access to ATMP therapy, and adaptive immune responses affecting product safety, efficacy and persistence

  • Capitalize on a biofluid repository from a diverse geographic/age/disease distribution to enable study of cellular and humoral immunity related to vector-based gene therapy
  • Assess and harmonize assays for humoral and cellular immunological responses to a range of vector-based gene therapies
  • Understand the clinical factors around pre-existing immunity limiting patient access to ATMP therapy
  • Characterize adaptive immune responses affecting gene therapy product safety, efficacy and persistence
  • Integrate clinical and laboratory data to disseminate safe and effective approaches to peri-treatment immunosuppression

Work package 5

Engagement with regulators

  • Identify opportunities for regulatory harmonization to accelerate ATMP product development
  • Engage with regulators and other stakeholders to ensure consortium-derived tools, methods and data support recommendations for regulatory harmonization and regulatory filings
  • Develop prospective databases and compile and analyze data to support regulatory harmonization and regulatory filings
  • Support biobank implementation and sustainability including ethical issues, confidentiality, data security, data harmonization and data analysis
  • Provide continuous regulatory and scientific support to facilitate success in all work packages