Periodic Reporting for period 3 - ARDAT (Accelerating Research & Development for Advanced Therapies)
Período documentado: 2022-11-01 hasta 2023-10-31
The overall objective of ARDAT is to develop and provide the data and tools to fill gaps in our knowledgebase in the areas of immunology and metabolism of viral gene/cell therapy to accelerate the research and development of Advanced Therapy Medicinal Products (ATMPs). 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 move these potentially transformative medicines forward more swiftly and to patients in need
Work Package 1: Establishment of management and reporting structures.
Work Package 2:
Completed assessment of the effects of rAAV9 transduction in terms of (a) modulation of gene expression of a panel of neuroinflammatory genes; and (b) remodelling of the secretory profile of the iNeurospheroid cultures, analysing several pro-inflammatory proteins and chemokines shown to be implicated in neuroinflammation.
Establishment of methods to determine T cell polyfunctionality from in vivo and 3D models using IsoLight technology and comparison with CyTOF. A proof-of-concept is completed and methodology will now be applied in 3D and mouse models.
An abstract summarizing the thus far collected data was submitted to the European Society of Gene and Cell Therapy meeting 2023 in Brussels. Data are currently being written into manuscript format and will likely be submitted by Q1 2024, for joint scientific publication. Despite small delays, the project is on track. In the next 12 months the focus will be on finishing the polyfunctional T cell analysis using samples available in house. In addition, the second focus will be on collaborations within WP2.4 and WP2.2 aiding 3D cell culture system research.
Work package 3:
Analytical assays for product characterisation have been developed and transfered from the UK based CRO Cell and Gene Therapy Catapult to the consortium.
Significant progress under Task 3.2.1 “Metabolism of the therapeutic vector genome in different cell types We have further improved our pipeline for data analysis resulting from ITR sequencing in AAV genomes by Oxford Nanopore sequencing.
Work package 4:
Completion of laboratory manual to establish standard operating procedures for sample handling and storage along with oversight from the Biorepository Governance Board.
Agreements between Partner Organisations for sample transfer in and out of the ARDAT biorepository are complete, allowing transfer of the first samples in Q1 2023
Establishment of a full battery of sample testing requirements and matching this with the assay capability across the consortium.
Signed material and data transfer agreement for the transfer of the samples to the ARDAT biobank. PFE, ULIV and USFD have signed this agreement.
Work package 5:
Comprehensive literature reviews in immunosuppression and pre-clinical protocols
Discussions with regulatory bodies to prepare the way for development of new treatments.
Two databases supporting the biodistribution/shedding whitepaper and another to support the ongoing immunogenicity and immunosuppression whitepaper. This will lead to the establishment of a comprehensive database for the curation and analysis of data generated from the project and to facilitate data-driven support e.g. guidance on clinical trial design, leveraging of information to waive nonclinical studies in certain situations, prediction of the consequences of pre-existing immunity and / or immune responses induced by a particular product, support for regulatory interactions beyond the duration of the project.
A Regulatory landscape assessment was published in April 2022.
A regulatory landscape survey was piloted at ESGCT in October 2022. it was shared with WP5 partners and results collated and discussed. Subsequently, the survey was shared internally within the consortium where it is hoped to canvas more academic partners.