Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, MD, USA.
Hemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration (FDA), Silver Spring, MD, USA.
Trends Mol Med. 2021 Nov;27(11):1074-1083. doi: 10.1016/j.molmed.2021.08.003. Epub 2021 Sep 4.
Recombinant therapeutic proteins are a broad class of biological products used to replace dysfunctional human proteins in individuals with genetic defects (e.g., factor VIII for hemophilia) or, in the case of monoclonal antibodies, bind to disease targets involved in cancers, autoimmune disorders, or other conditions. Unfortunately, immunogenicity (immune response to the drug) remains a key impediment, potentially affecting the safety and efficacy of these therapeutics. Immunogenicity risk is routinely evaluated during the licensure of therapeutic proteins. However, despite eliciting anti-drug immune responses in at least some patients, most protein drugs are nevertheless licensed as they address unmet medical needs. The pre-licensure immunogenicity assessments of therapeutic proteins are the subject of numerous reviews and white papers. However, observation and clinical management of the immunogenicity of approved therapeutic proteins face additional challenges. We survey the immunogenicity of approved therapeutic proteins, discuss the clinical management of immunogenicity, and identify the challenges to establishing clinically relevant immunogenicity assays for use in routine clinical practice.
重组治疗性蛋白是一类广泛应用的生物制品，用于替代具有遗传缺陷（如血友病的因子 VIII）的个体中功能失调的人类蛋白，或者在单克隆抗体的情况下，与癌症、自身免疫性疾病或其他疾病相关的疾病靶点结合。不幸的是，免疫原性（对药物的免疫反应）仍然是一个关键障碍，可能会影响这些治疗药物的安全性和疗效。在治疗性蛋白的许可过程中，通常会评估免疫原性风险。然而，尽管在至少一些患者中引发了抗药物免疫反应，但由于大多数蛋白药物都能满足未满足的医疗需求，因此仍被批准上市。治疗性蛋白的预许可免疫原性评估是许多综述和白皮书的主题。然而，批准的治疗性蛋白的免疫原性的观察和临床管理面临着额外的挑战。我们调查了已批准的治疗性蛋白的免疫原性，讨论了免疫原性的临床管理，并确定了在常规临床实践中建立具有临床相关性的免疫原性检测方法的挑战。
