Pseudomonas aeruginosa 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.
Keywords: P. aeruginosa exotoxin A (PE); cancer; cancer resistance; immunogenicity; immunotoxins (ITs); radiotherapy; structural optimization.
Exotoxin A-immunotoxins are proteins that have been used in cancer treatments. The building components of these proteins are very poisonous to both cancer and normal cells. Also, unfavorable body reactions and side effects were seen with their usage. To allow the safe use of these proteins, changes were made in their building components. These changes made them damaging only to cancer cells while being safe to normal non-cancerous cells. This review will talk about the use of exotoxin A-Immunotoxins in different cancer treatments, and how they are created to limit the poisonous effect of their building components to only cancer cells.