Freeline AAVS3 Neutralizing Antibody Test
Research type
Research Study
Full title
Characterisation of AAVS3 Transduction Inhibition Assay using stored clinical samples
IRAS ID
303667
Contact name
Jonathan Foley
Contact email
Sponsor organisation
Freeline Therapeutics
Clinicaltrials.gov Identifier
SOP22021, FL AAVS3 Transduction Inhibition Assay Method
Duration of Study in the UK
0 years, 3 months, 0 days
Research summary
Owing to their non- pathogenic nature and outstanding safety record, adeno- associated virus (AAV) vectors have become the gene therapy vector of choice. However, up to 70% of people will be exposed to at least one strain of AAV during their lives and their anti-AAV antibodies can inhibit effective delivery of the therapeutic vector to target cells. Therefore, a suitable method of characterising these antibodies is of paramount importance to ensure safe and beneficial inclusion of patients for gene therapy treatment. In our earlier phase 1/2 clinical trial, we used a FACS-based transduction inhibition assay to determine clinical trial eligibility. All patients that were enrolled into the clinical study were successfully transduced with AAV vector and achieved meaningful expression of the therapeutic protein of interest, thus confirming that patients below the cut-point for the FACS-assay had no/ negligible neutralising antibodies in their blood at the time of treatment. To enable broader enrolment in future trials and aftermarket authorisation, a screening assay with higher throughput is required. In the proposed study we will use the novel assay method to characterise neutralising antibody titres in separate aliquots of samples previously tested using the FACS-method. Since the therapeutic protein expression levels are already known, the data generated will enable us to bridge from the FACS-based assay to novel method, which will enable broader enrolment of patients.
REC name
Yorkshire & The Humber - South Yorkshire Research Ethics Committee
REC reference
21/YH/0197
Date of REC Opinion
13 Aug 2021
REC opinion
Favourable Opinion