Periodic Reporting for period 4 - ARDAT (Accelerating Research & Development for Advanced Therapies)
Berichtszeitraum: 2023-11-01 bis 2024-10-31
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 formed the basis of D2.3.
Establishment of methods to determine T cell polyfunctionality from in vivo and 3D models produced the publication; doi:10.3389/fimmu.2024.1450524.
By using anti-IdeS mAbs generated by the consortium, quantitation of anti-IdeS IgG and IgA in the plasma & serum of healthy individuals was completed.
Work package 3:
Analytical assays for product characterisation have been developed & transferred from the UK based CRO Cell and Gene Therapy Catapult to the consortium.
Progress under Task 3.2.1 further improving our pipeline for data analysis resulting from ITR sequencing in AAV genomes by Oxford Nanopore sequencing.
Development of a pipeline to characterise the modification preferences of the current globalized editing methodology.
D3.1: “Identification of factors with key role in vector genome dilution in models of liver diseases” was submitted.
Cell line assays suggest the potential immune evasion ability of glyco-AAV9 vectors, next steps will extend into in vivo systems.
AAV9-based gene replacement for SPG47 resulted in several outputs; a publication; doi:10.1038/s44321-024-00148-5 patent filing, IND submitted to FDA and a start-up company (BlackfinBio).
Work package 4:
Completion of laboratory manual to establish procedures for sample handling and storage along with oversight from the Biorepository Governance Board.
Agreements between Partner Organisations for sample transfer in & out of the ARDAT biorepository completed, allowing the transfer of samples to the ARDAT Biobank.
Establishment of a full battery of sample testing requirements and matching this with the assay capability across the consortium.
PFE, ULIV and USFD signed MDTA for the transfer of samples to the ARDAT biobank.
Full ethical approval from the Health Research Authority (HRA) for the ARDAT Biobank at the USFD.
A review of current immunosuppressive protocols used in AAV gene therapy has been published; doi:10.1016/j.ymthe.2024.07.016.
Negotiations ongoing with the UK National Health Service (NHS) to secure patient samples from individuals treated with AAV9-based gene therapy, Zolgensma. Alongside accessing samples from patients treated with AAV5.
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 to support the 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.
A Regulatory landscape assessment was published in April 2022 and a regulatory landscape survey piloted at ESGCT in October 2022 this was shared with WP5 partners and results collated & discussed. Subsequently, the survey was shared internally to canvas more academic partners.
D5.13: "Whitepaper 2 (immunosuppression protocols)" was submitted. Cell Report Medicine has invited full paper for consideration.