Immunogenicity testing for gene therapy
Thursday 18 September 2025
07:00 [PDT] 10:00 [EDT] 15:00 [BST]
The immunogenicity of gene therapy is a rapidly evolving area, with significant progress in both understanding and mitigating immune responses.
Recent lessons in immunogenicity testing for gene therapy highlight the need to reassess the traditional multi-tiered paradigm, emphasizing efficiency without compromising patient safety. Regulatory feedback underscores the importance of risk-based development and validation of TAb/NAb assays, with a preference for cell-based formats and early implementation in high-risk scenarios. When compiling the Integrated Summary of Immunogenicity (ISI), sponsors should adopt a structured, risk-focused approach that integrates assay strategy, clinical impact, and mitigation plans, aligning with FDA and EMA expectations to support regulatory decision-making and product lifecycle management.
What will you learn?
-
Pre-existing anti-AAV antibodies are common (30–60%) and can significantly impact the safety and efficacy of gene therapy, making their detection critical before treatment.
-
Total Antibody (TAb) vs. Neutralizing Antibody (NAb) assays offer different insights—TAb assays are more sensitive and high-throughput, while NAb assays provide functional relevance but are more complex and costly.
-
Signal-to-Noise (S/N) ratio is emerging as a faster, resource-efficient alternative to traditional titer-based methods, especially for patient enrollment and monitoring in gene therapy trials.
-
Direct-to-Titer testing may streamline workflows by bypassing traditional screening and confirmatory steps, though its clinical acceptance and validation remain key challenges.
-
Positive controls are essential for assay reliability, with humanized monoclonal antibodies preferred over animal-derived ones for gene therapy applications to ensure consistency and relevance.
Who may this interest?
-
Clinical Scientists and Translational Researchers
-
Regulatory Affairs Specialists
-
Bioanalytical Scientists
-
Biotech and Pharma R&D Teams
-
Clinical Trial Managers
In association with:
