用于治疗创新的工程化生长因子配体和受体。
Engineering growth factor ligands and receptors for therapeutic innovation.
作者信息
An Xinran, Paoloni Justin, Oh Yuseong, Spangler Jamie B
机构信息
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
出版信息
Trends Cancer. 2024 Dec;10(12):1131-1146. doi: 10.1016/j.trecan.2024.09.006. Epub 2024 Oct 10.
Growth factors signal through engagement and activation of their respective cell surface receptors to choreograph an array of cellular functions, including proliferation, growth, repair, migration, differentiation, and survival. Because of their vital role in determining cell fate and maintaining homeostasis, dysregulation of growth factor pathways leads to the development and/or progression of disease, particularly in the context of cancer. Exciting advances in protein engineering technologies have enabled innovative strategies to redesign naturally occurring growth factor ligands and receptors as targeted therapeutics. We review growth factor protein engineering efforts, including affinity modulation, molecular fusion, the design of decoy receptors, dual specificity constructs, and vaccines. Collectively, these approaches are catapulting next-generation drugs to treat cancer and a host of other conditions.
生长因子通过与各自的细胞表面受体结合并激活来发出信号，从而编排一系列细胞功能，包括增殖、生长、修复、迁移、分化和存活。由于它们在决定细胞命运和维持体内平衡方面的关键作用，生长因子信号通路的失调会导致疾病的发生和/或进展，尤其是在癌症背景下。蛋白质工程技术的惊人进展使得创新策略能够将天然存在的生长因子配体和受体重新设计为靶向治疗药物。我们综述了生长因子蛋白质工程方面的工作，包括亲和力调节、分子融合、诱饵受体设计、双特异性构建体和疫苗。总的来说，这些方法正在推动新一代药物用于治疗癌症和许多其他疾病。
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