CD8+ T-cell responses to adeno-associated virus capsid in humans

By F. Mingozzi, M. Maus, Daniel J. Hui, D. Sabatino, Samuel L. Murphy, J. Rasko, M. Ragni, C. Manno, J. Sommer, Haiyan Jiang and 3 more. Nature Medicine, 2007

736 citations recorded by the source corpus.

Subfields: Epidemiology, Genetics, Oncology

View Paper: https://www.semanticscholar.org/paper/0b1a952e25de5e74d5aab9aa83534deec0865881

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In Genetics

1. F. Mingozzi

Citations in the corpus

• Immune responses to AAV vectors: overcoming barriers to successful gene therapy. (2013, neutral): “activation leads to clearance of AAV-transduced cells.(67) Human studies show expansion of capsid T cells”
• Current Clinical Applications of In Vivo Gene Therapy with AAVs (2020, background): “Part of this variability may be explained, in part, by a hypothesized cellular immune response to capsid peptides presented by transduced hepatocytes that can result in reduced or loss of transgene expression, thereby limiting efficacy.(214) Additionally, vector CpG motifs may potentially be immune ”
• Gene therapy comes of age (2018, neutral): “Subsequent studies revealed that expression of the factor IX transgene in humans was of short duration because of an immune response to the AAV capsid (42).”
• Emerging Issues in AAV-Mediated In Vivo Gene Therapy (2017, background): “These observations were associated with the expansion of capsid-specific CD8 T cells, which likely were responsible for the immune rejection of the transduced hepatocytes.(58)”
• Immune Responses to Viral Gene Therapy Vectors (2020, background): “CD8 T Cell Responses to Capsid In the first liver-directed gene therapy trial with AAV vectors (performed with an AAV2 vector in patients with hemophilia B), a loss of factor IX transgene expression and transient mild elevations of liver enzymes in circulation were correlated with a CD8 T cell respo”
• Prevalence of Serum IgG and Neutralizing Factors Against Adeno-Associated Virus (AAV) Types 1, 2, 5, 6, 8, and 9 in the Healthy Population: Implications for Gene Therapy Using AAV Vectors (2010, neutral): “Indeed, AAV2 capsid-primed CD8 þ memory T cells in humans cross-react with epitopes from AAV8 and AAV1 capsid and result in expansion of functional CD8 þ cytotoxic lymphocytes that are indistinguishable from those elicited by AAV2 capsid epitopes (Mingozzi et al. , 2007a).”
• Identification of Pre-Existing Adaptive Immunity to Cas9 Proteins in Humans (2018, neutral): “In prior gene therapy trials in which patients had pre-existing adaptive immune responses to the viral vector, no therapeutic benefit was derived from the therapy due to either neutralization of the vector by antibodies (21, 22) or clearance of transduced cells by cytotoxic Tlymphocytes (CTLs) (23).”