评估和减轻治疗性蛋白的免疫原性。
Evaluating and Mitigating the Immunogenicity of Therapeutic Proteins.
机构信息
Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapeutics, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA.
Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapeutics, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA.
出版信息
Trends Biotechnol. 2018 Oct;36(10):1068-1084. doi: 10.1016/j.tibtech.2018.05.008. Epub 2018 Jun 13.
Therapeutic proteins provide interventions for some of the most complex and intractable diseases and are an essential part of modern medicine. Immunogenicity is the development of immune responses, usually measured by antibodies, to therapeutic proteins. These responses can adversely affect the safety and efficacy of the therapeutic agent and may have the following consequences: neutralization of a life-saving biotherapeutic, crossreactivity to non-redundant endogenous proteins, and hypersensitivity responses. These concerns have been underscored by the discontinuation of development of several drugs in recent years owing to immunogenicity issues. We review here recent progress in technological approaches that are useful for the clinical and non-clinical risk assessment of immunogenicity as well as mitigation strategies including deimmunizing protein molecules and inducing immune tolerance to the therapeutic protein.
治疗性蛋白为一些最复杂和棘手的疾病提供了干预手段，是现代医学的重要组成部分。免疫原性是指针对治疗性蛋白产生免疫反应，通常用抗体来衡量。这些反应可能会对治疗剂的安全性和有效性产生不利影响，并可能产生以下后果：中和救命的生物治疗药物、与非冗余内源性蛋白质发生交叉反应，以及产生过敏反应。近年来，由于免疫原性问题，一些药物的开发已经停止，这突显了这些问题的重要性。我们在这里回顾了近年来在技术方法方面的进展，这些方法对于临床和非临床免疫原性风险评估以及缓解策略（包括使蛋白分子去免疫原化和诱导对治疗性蛋白的免疫耐受）都非常有用。
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