ArticleMolecular therapy. Methods & clinical development2021
Monitoring cell-mediated immune responses in AAV gene therapy clinical trials using a validated IFN-γ ELISpot method.
Article in Molecular therapy. Methods & clinical development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- A phase 1/2 safety and efficacy study of TAK-754 gene therapy: The challenge of achieving durable factor VIII expression in haemophilia A clinical trials.Haemophilia : the official journal of the World Federation of Hemophilia · 2025Trial
- Clinical immunogenicity outcomes from GENEr8-1, a phase 3 study of valoctocogene roxaparvovec, an AAV5-vectored gene therapy for hemophilia A.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Trial
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- Host Endoplasmic Reticulum Stress and Interferon Responses Contribute to AAV-Induced Ocular Toxicity.bioRxiv : the preprint server for biology · 2026Article
- Immunogenicity in Approved Adeno-Associated Virus-Based Gene Therapies: A Framework for a Tailored Assessment Strategy.The AAPS journal · 2026Review
- Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Immune Response Associated Hepatotoxicity in Hemophilia Gene Therapy: Mechanisms, Management, and Challenges.Journal of hematology · 2026Review
- Cellular Immunogenicity Assessments in CAR-T Cell Therapies: Current Insights and Future Directions.The AAPS journal · 2025Article
- Challenges in Humoral Immune Response to Adeno-Associated Viruses Determination.International journal of molecular sciences · 2025Review
- Adeno-associated virus-based gene therapy for hemophilia-addressing the gaps.Research and practice in thrombosis and haemostasis · 2025Review
- Immune responses in retinal gene therapy: challenges, mechanisms, and future strategies.Frontiers in immunology · 2025Review
- Validation of an interferon-gamma enzyme-linked immunosorbent spot assay to evaluate cell-mediated immunity against severe acute respiratory syndrome coronavirus 2.Human vaccines & immunotherapeutics · 2024Article
- Multicenter assessment and longitudinal study of the prevalence of antibodies and related adaptive immune responses to AAV in adult males with hemophilia.Gene therapy · 2024Article
- Polyfunctional T cells and unique cytokine clusters imprint the anti rAAV2/rAAV9 vector immune response.Frontiers in immunology · 2024Article
- Important Considerations for ELISpot Validation.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Performance and Stability of New Class of Fetal Bovine Sera (FBS) and Its Lyophilized Form in ELISpot and FluoroSpot Assays: Applications for Monitoring the Immune Response in Vaccine, and Cell and Gene Immunotherapy in Clinical Trials.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Innate and adaptive AAV-mediated immune responses in a mouse model of Duchenne muscular dystrophy.Molecular therapy. Methods & clinical development · 2023Article
- Evaluation of Cellular Immune Response to Adeno-Associated Virus-Based Gene Therapy.The AAPS journal · 2023Review
- Low cross reactivity between wild type and deamidated AAV can lead to false negative results in immune monitoring T-cell assays.Frontiers in immunology · 2023Article
- Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper.Molecular therapy. Methods & clinical development · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adeno-associated virus (AAV)-based gene therapies have recently shown promise as a novel treatment for hereditary diseases. Due to the viral origin of the vector capsid, however, cellular immune response may be elicited that could eliminate transduced target cells. To monitor cellular immune responses in clinical trials, we optimized and bioanalytically validated a sensitive, robust, and reliable interferon-γ (IFN-γ) enzyme-linked immunospot (ELISpot) assay. For method performance validation, human peripheral blood mononuclear cells (PBMCs) were stimulated with peptides derived from AAV5 capsid proteins and the encoded transgene product, human blood clotting factor VIII (FVIII), in addition to positive controls, such as peptides from the 65-kDa phosphoprotein of cytomegalovirus. We statistically assessed the limit of detection and confirmatory cutpoint, evaluated precision and linearity, and confirmed specificity using HIV peptides. Robustness parameter ranges and sample stability periods were established. The validated IFN-γ ELISpot assay was then implemented in an AAV5-FVIII gene therapy clinical trial. Cellular immune responses against the AAV5 capsid were observed in most participants as soon as 2 weeks following dose administration; only limited responses against the transgene product were detected. These data underscore the value of using validated methods for monitoring cellular immunity in AAV gene therapy trials.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.