Immunogenicity Assessment of AAV-based Gene Therapies: An IQ Consortium Industry White Paper

Overview

Journal Mol Ther Methods Clin Dev

Publisher Cell Press

Date 2022 Sep 12

PMID 36092368

Authors

Tong-Yuan Yang

Manuela Braun

Wibke Lembke

Fraser McBlane

John Kamerud

Stephen DeWall

Edit Tarcsa

Xiaodong Fang

Lena Hofer

Uma Kavita

Vijay V Upreti

Swati Gupta

LiNa Loo

Alison J Johnson

Rakesh Kantilal Chandode

Kay-Gunnar Stubenrauch

Maya Vinzing

Cindy Q Xia

Vibha Jawa

Affiliations

Soon will be listed here.

Abstract

Immunogenicity has imposed a challenge to efficacy and safety evaluation of adeno-associated virus (AAV) vector-based gene therapies. Mild to severe adverse events observed in clinical development have been implicated with host immune responses against AAV gene therapies, resulting in comprehensive evaluation of immunogenicity during nonclinical and clinical studies mandated by health authorities. Immunogenicity of AAV gene therapies is complex due to the number of risk factors associated with product components and pre-existing immunity in human subjects. Different clinical mitigation strategies have been employed to alleviate treatment-induced or -boosted immunogenicity in order to achieve desired efficacy, reduce toxicity, or treat more patients who are seropositive to AAV vectors. In this review, the immunogenicity risk assessment, manifestation of immunogenicity and its impact in nonclinical and clinical studies, and various clinical mitigation strategies are summarized. Last, we present bioanalytical strategies, methodologies, and assay validation applied to appropriately monitor immunogenicity in AAV gene therapy-treated subjects.

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