Immunogenicity testing for gene therapy
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?
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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.
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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.
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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.
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Direct-to-Titer testing may streamline workflows by bypassing traditional screening and confirmatory steps, though its clinical acceptance and validation remain key challenges.
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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?
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Clinical Scientists and Translational Researchers
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Regulatory Affairs Specialists
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Bioanalytical Scientists
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Biotech and Pharma R&D Teams
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Clinical Trial Managers
David Escobar
Associate Director, Ligand Binding Assay Technologies
Navigate BioPharma Services, Inc. (a Novartis Subsidiary) (CA, USA)
Originally from La Paz, Bolivia, David emigrated to the USA in 1988. He received his BS in molecular biology from San Diego State University (CA, USA) in 1998. He has been fortunate to interact and learn from talented scientists from all walks of life. He joined the bioanalytical world in 2006, conducting pharmacokinetic and immunogenicity evaluations. 11 years and countless validations later, he joined Navigate BioPharma Services in 2017, where he is currently the manager for the ligand binding group.
This webinar was recorded on the 14th of October 2025.
