WHO/BS/2019.2373 Proposed WHO 1st Inter Reference Panel (19/158) for Quantitation of Lentiviral Vector Integration Copy Numbers

Overview

This report describes the development and characterisation of four candidate materials and evaluation of their suitability to serve as WHO standards for lentiviral vector (LV) integration analysis. The development of the 1st WHO standard for lentiviral vector integration is to meet a high demand from the community to ensure delivery of a safe and efficacious dose of LV products to patients and to facilitate patient follow-up worldwide. The materials comprise human genomic DNA containing zero, low or high copies of a lentiviral vector integration. The lentiviral vector integration copy number per cell was determined in an international collaborative study using three principal methods: TaqMan qPCR, SYBRGreen qPCR and digital PCR, and supplementary sequencing-based methods. A total of thirty-one laboratories from fifteen countries participated in the collaborative study, including eight National Regulatory/Control laboratories; six academic laboratories/hospitals and seventeen companies (Table 1). Based on the results obtained in this study, three of the candidate materials are proposed as a reference panel for LV copy number with assigned values of 0 LV copies/cell (coded 18/142), 1.42 LV copies/cell for the low value material (coded 18/126) and 8.76 LV copies/cell for the high value material (coded 18/132) It is also proposed that the other candidate material (coded 18/144) is established as a stand-alone qualitative reference reagent for the integration site analysis, with 10 defined integration sites.