What question did this study set out to answer?

To review the immunological barriers and severe toxicities linked to adeno-associated viral (AAV) vector gene therapy, particularly at high doses.

August 12, 2022SHILAP Revista de lepidopterologíaOpen Access

Immunogenicity and toxicity of AAV gene therapy

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Authors

HEHildegund C.J. ErtlThe Wistar Institute

Discussion

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Implication

Narrative review reveals severe immune-mediated toxicities in high-dose viral vector recipients, highlighting the need for dose-sparing designs and repeated dosing strategies.

Key Points

To review the immunological barriers and severe toxicities linked to adeno-associated viral (AAV) vector gene therapy, particularly at high doses.
Synthesized clinical and preclinical findings regarding adaptive and innate immune responses against AAV capsids and transgene products.
Evaluated pathological mechanisms of organ toxicity, complement cascade activation, and immunosuppressive regimen failures in high-dose gene transfer protocols.
Immune complications include destructive T cell responses that resist standard immunosuppressive regimens, as well as systemic innate complement activation causing serious adverse events.
Very high vector doses precipitate severe organ toxicities, specifically life-threatening hepatotoxicity and dorsal root ganglia toxicity.
Proposed solutions focus on engineering hyper-efficient vectors for dose reduction, or administering divided low doses combined with targeted antibody or B-cell depletion.

Cite This Study

Hildegund C.J. Ertl (2022) studied this question.

synapsesocial.com/papers/69d7429658d71cbec648f5a6 https://doi.org/10.3389/fimmu.2022.975803

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August 12, 2022SHILAP Revista de lepidopterologíaOpen Access

Immunogenicity and toxicity of AAV gene therapy

View Full Paper

Ask AI

Bookmark

Authors

HEHildegund C.J. ErtlThe Wistar Institute

Discussion

Member takes

Implication

Narrative review reveals severe immune-mediated toxicities in high-dose viral vector recipients, highlighting the need for dose-sparing designs and repeated dosing strategies.

Key Points

To review the immunological barriers and severe toxicities linked to adeno-associated viral (AAV) vector gene therapy, particularly at high doses.
Synthesized clinical and preclinical findings regarding adaptive and innate immune responses against AAV capsids and transgene products.
Evaluated pathological mechanisms of organ toxicity, complement cascade activation, and immunosuppressive regimen failures in high-dose gene transfer protocols.
Immune complications include destructive T cell responses that resist standard immunosuppressive regimens, as well as systemic innate complement activation causing serious adverse events.
Very high vector doses precipitate severe organ toxicities, specifically life-threatening hepatotoxicity and dorsal root ganglia toxicity.
Proposed solutions focus on engineering hyper-efficient vectors for dose reduction, or administering divided low doses combined with targeted antibody or B-cell depletion.

Cite This Study

Hildegund C.J. Ertl (2022) studied this question.

synapsesocial.com/papers/69d7429658d71cbec648f5a6 https://doi.org/10.3389/fimmu.2022.975803

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