Evaluation of developmental and efficacy of Pseudomonas exotoxin-based immunotoxins on brain tumors
Evaluation of developmental and efficacy of Pseudomonas exotoxin-based immunotoxins on brain tumors
Mona Adel,1,*Sina Parvaneh,2
1. Islamic Azad University, Tehran East Branch 2. Islamic Azad University, Central Tehran branch
Introduction: Throughout history, cancer has attracted global health concern. This disease affects different target tissues, of which brain tumors are among the most dangerous. Microorganisms are one of the factors that transform normal cells into cancer cells. Due to the many side effects of traditional treatments, the world is looking for an alternative, more effective solution to treat this disease, the use of genetically modified microorganisms, which are hybrid molecules that are attached to bacterial or plant toxins to carriers of the genus Antibodies are formed that are linked by chemical bonding or genetic engineering to destroy pathological cells in various fields such as cancer, immune diseases or pain control. Penetration of protein drugs into the brain is very difficult due to the presence of protective barriers. The purpose of the current research is to investigate RIT derived from Pseudomonas Aeruginosa (PE), especially NBI-3001, which is an intravenous immunotoxin for the treatment of malignant glioma.
Methods: An online search of published medical articles through PubMed, Scopus, Web of Science, and Google Scholar using the terms "cancer," "brain tumor," "GBM," "Pseudomonas," "immunotoxin," "PE38," "NBI- 3001" were reviewed and screened and after evaluating the validity of the articles using SJR and MDPI databases, finally, more than 20 articles were carefully reviewed.
Results: Cancer is the cause of one of the six deaths in the world. But today, about 40% of cancers can be prevented, and with timely diagnosis, more than 80% of them can be treated with the help of new approaches. Many studies have been conducted on bacteria and their molecular mechanisms. The findings have shown that the cause of carcinogenesis is their continuous infection, and through this feature, they are used in cancer treatment. Brain tumors are one of the most dangerous diseases that can damage the brain and cause death. The cause of this type of cancer is a genetic mutation that leads to a change in tissue function. Glioblastoma in adults and medulloblastoma in children are the most common and aggressive malignant tumors. Patients with high-grade astrocytic tumors require new therapeutic approaches due to the highly heterogeneous and diffuse nature of astrocytic tumors. Advances in genomic and proteomic research have paved the way for personalized treatment based on the characteristics of the target tumor and its environment. Treatment with living bacteria that target the tumor is a unique option because, in many treatment methods, the genetic structure of the tumor is effective in the treatment, but the effect of this method is on the depths of the tumor. It starts to multiply by selective colonization in the tumor, while in the rest of the body, it is cleared after a few days. The protective barriers of the brain make it difficult for the drug to penetrate. We discuss 2 new approaches to this problem: 1. blocking immune checkpoints 2. local treatment by new immunotoxins (RIT) and drug injection directly into the tumor. The high efficiency of RITs is due to factors such as very small molecular size, which makes it easier to penetrate solid tumors. Second, while retaining the specificity of Monoclonal antibodies, they have become more potent and have no known mechanism of drug resistance. Third, RITs can effectively kill quiescent, non-dividing cells, different from traditional chemotherapies. Finally, RITs have little cross-resistance with other agents and are also resistant to chemotherapy in cancer.
Conclusion: Due to their unique characteristics, recombinant immunotoxins are the best alternative or companion to traditional methods and a promising method for treating GBM. Since RIT-based treatment methods are considered a new platform in the treatment of brain tumors, cognition and understanding of this treatment method is It makes it possible for scientists to Development this method and discover its complementary steps and eliminate the complications caused by this treatment method. The current research examines therapeutic approaches based on RITs.