Abstract:
The introduction and development of biologics such as therapeutic proteins, gene-, and cell-based therapy have revolutionized the scope of treatment for many diseases. However, a significant portion of the patients develop unwanted immune reactions against these novel biological modalities, referred to as immunogenicity, and no longer benefit from the treatments. In the current review, using Hemophilia A (HA) therapy as an example, we will discuss the immunogenicity issue of multiple biological modalities. Currently, the number of therapeutic modalities that are approved or recently explored to treat HA, a hereditary bleeding disorder, is increasing rapidly. These include, but are not limited to, recombinant factor VIII proteins, PEGylated FVIII, FVIII Fc fusion protein, bispecific monoclonal antibodies, gene replacement therapy, gene editing therapy, and cell-based therapy. They offer the patients a broader range of more advanced and effective treatment options, yet immunogenicity remains the most critical complication in the management of this disorder. Recent advances in strategies to manage and mitigate immunogenicity will also be reviewed.
摘要:
治疗性蛋白质等生物制剂的引进和开发,基因-,和基于细胞的治疗彻底改变了许多疾病的治疗范围。然而,很大一部分患者会对这些新的生物学模式产生不必要的免疫反应,称为免疫原性,不再从治疗中受益。在当前的审查中,以血友病A(HA)治疗为例,我们将讨论多种生物学模式的免疫原性问题。目前,批准或最近探索用于治疗HA的治疗方式的数量,遗传性出血性疾病,正在迅速增加。这些包括,但不限于,重组因子VIII蛋白,聚乙二醇化FVIII,FVIIIFc融合蛋白,双特异性单克隆抗体,基因替代疗法,基因编辑疗法,和基于细胞的治疗。他们为患者提供更广泛的更先进和有效的治疗选择,然而,免疫原性仍然是本病治疗中最关键的并发症.还将审查管理和减轻免疫原性的策略的最新进展。