Wolfgang Miesbach: Immune-Engineered AAV Capsids Displaying IL-10 Enhance Gene Therapy Safety and Efficacy
Wolfgang Miesbach, Head of Hemostasis/Hemophilia Center at Medical Clinic 2 at University Hospital Frankfurt, shared a post on LinkedIn:
“Don’t suppress the immune system.
Teach it.
ESGCT26, Carmen Unzu on leveraging immune recognition for safer and more potent AAV gene therapy.
IL-10 is one of the body’s own brakes on inflammation: a cytokine that dampens pro-inflammatory signalling, limits antigen presentation and T-cell activation, and favours regulatory T cells.
Tolerance rather than suppression.
Anti-AAV immunity costs us at every stage.
Neutralising antibodies exclude patients before dosing, immune recognition erodes efficacy and safety during treatment, and the antibody response afterwards closes the door on re-dosing.
Our current answer is pharmacological immunosuppression: broad, prolonged, with a side-effect profile of its own.
The concept: build the immunomodulation into the vector itself rather than give it as a separate drug.
Two routes, compared in mice: an IL-10-derived peptide displayed genetically on the AAV8 capsid, acting transiently from the moment of dosing; or AAV-mediated IL-10 expression from the genome, sustained and transgene-dependent.
Her conclusions: incorporating an immunomodulatory agent into the capsid was sufficient to induce a durable immune change, and transient peptide display enhanced transgene expression while selectively reducing AAV immunogenicity after systemic administration.”
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