Abstract 3288: The use of in vitro assays to assess and measure gene therapy immunogenicity

Abstract

Abstract Introducing the gene therapy product into human cells requires a vector that will deliver the gene into the cells and incorporate those genes into the gene expression mechanism in those cells. One of the issues is the induction of an unwanted immune response that can have an influence on the efficacy and potency of the treatment. Additionally, pre-existing immunity towards AAV and CRISPR can also neutralize the therapeutic effect. Comprehensive assessment of human immune responses to gene therapy candidates includes characterization of humoral and cellular immunogenicity specific for both the viral vector and the expressed transgene (protein) product before and after dose administration. In vitro assays such as dendritic cell activation and T cell proliferation assays can be used to assess this unwanted immunogenicity in an early phase. Additionally, innate assays such as dendritic cell activation assays can be used for the evaluation of potential impurities and innate response inducing contaminants. Sensitive Fluorospot assays can be used to monitor patient’ specific immunogenicity both at the T and B cell level. The advantage of the Fluorospot technology is the sensitivity to detect responses on a single cell level and measure up to 4 analytes simultaneously. For all in vitro assays, the quality and functionality of the primary cells is important to assure reproducibility and solid assay performance. Citation Format: Jana Schockaert, Thibaut J. Janss, Juliette Lamy, Aurélie Mazy, Ellen Boelen, Simon Lefevre, Sofie Pattijn. The use of in vitro assays to assess and measure gene therapy immunogenicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3288.