Morgan Radwa N, Saleh Sarra E, Farrag Hala A, Aboshanab Khaled M
National Centre for Radiation Research & Technology (NCRRT), Drug Radiation Research Department, Egyptian Atomic Energy Authority (EAEA), Ahmed El-Zomor Street, Nasr city, Cairo, 11787, Egypt.
Microbiology & Immunology Department, Faculty of Pharmacy, Ain Shams University, African union organization Street, Abbassia, Cairo, 11566, Egypt.
Ther Deliv. 2023 Jan;14(1):31-60. doi: 10.4155/tde-2022-0055. Epub 2023 Mar 23.
exotoxin A-based immunotoxins (PE-ITs) are fusion proteins that harness targeting and toxin moieties. Structural optimizations in PE and targeting moieties were implemented to lower their immunogenicity and alleviate undesirable side effects. PE moiety was engineered to lack its cell-binding domain and T cell epitope regions, whereas single chain (scFv) and disulfide Fv portions (dsFv), nanobodies, and monobodies were utilized as targeting moieties. This review discusses applications of PE-ITs on different types of cancer, structural optimizations to reduce PE-ITs drawbacks, and recent modifications applied for efficient therapeutic delivery. Finally, we draw attention to the possibility of combining radiotherapy, radionuclides, and RGDs with PE-IT to improve overall response rates of IT-based treatments and reduce cancer cell resistance.
基于外毒素A的免疫毒素（PE-ITs）是利用靶向部分和毒素部分的融合蛋白。对PE和靶向部分进行了结构优化，以降低其免疫原性并减轻不良副作用。对PE部分进行工程改造，使其缺乏细胞结合结构域和T细胞表位区域，而单链（scFv）和二硫键Fv部分（dsFv）、纳米抗体和单域抗体被用作靶向部分。本文综述了PE-ITs在不同类型癌症中的应用、减少PE-ITs缺点的结构优化以及为实现有效治疗递送而进行的最新修饰。最后，我们提请注意将放疗、放射性核素和RGDs与PE-IT相结合以提高基于IT的治疗的总体反应率并降低癌细胞耐药性的可能性。
