高剂量全身 AAV 治疗中的致命免疫毒性。
Lethal immunotoxicity in high-dose systemic AAV therapy.
机构信息
Department of Molecular Microbiology and Immunology and Department of Neurology, School of Medicine, Department of Biomedical Sciences, College of Veterinary Medicine, Department of Chemical and Biomedical Engineering, College of Engineering, University of Missouri, Columbia, MO 65212, USA.
出版信息
Mol Ther. 2023 Nov 1;31(11):3123-3126. doi: 10.1016/j.ymthe.2023.10.015. Epub 2023 Oct 10.
Abstract
High-dose systemic gene therapy with adeno-associated virus (AAV) is in clinical trials to treat various inherited diseases. Despite remarkable success in spinal muscular atrophy and promising results in other diseases, fatality has been observed due to liver, kidney, heart, or lung failure. Innate and adaptive immune responses to the vector play a critical role in the toxicity. Host factors also contribute to patient death. This mini-review summarizes clinical findings and calls for concerted efforts from all stakeholders to better understand the mechanisms underlying lethality in AAV gene therapy and to develop effective strategies to prevent/treat high-dose systemic AAV-gene-therapy-induced immunotoxicity.
摘要
高剂量系统性腺相关病毒（AAV）基因治疗正在临床试验中用于治疗各种遗传性疾病。尽管在脊髓性肌萎缩症方面取得了显著成功，并且在其他疾病方面也取得了有希望的结果，但由于肝脏、肾脏、心脏或肺部衰竭，仍观察到了死亡率。载体的固有和适应性免疫反应在毒性中起着关键作用。宿主因素也导致患者死亡。本综述总结了临床发现，并呼吁所有利益相关者共同努力，以更好地了解 AAV 基因治疗致死性的潜在机制，并制定有效的策略来预防/治疗高剂量系统性 AAV 基因治疗引起的免疫毒性。
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