Design and analysis of a new immunogenic structure based on natural toxins in the treatment of cancer using bioinformatics tools

cancers are one of the most common diseases known worldwide that have many tissue and structural heterogeneities that make the treatment process difficult. Breast cancer is one of the most well-known, and many patients with it are HER2 positive. Conventional cancer treatments today are not effective enough in preventing death. Immunotoxins are hybrid molecules that contain a part of the immune system, one antibody or a binding part of the antibody, and the other part is a toxic part. In this study, we seek to design a new immunotoxin, including the anti-HER2 receptor, trastuzumab, derived from a single-strand variable fragment (scFv) that binds to a functional part of a spider family venom called a neurotoxin.

We examined the physicochemical properties, secondary structure and solubility of chimeric proteins using ProtParam, PepCalc, respectively. A 3D model of the hybrid protein was created using I-TASSER servers. Then its structure and solubility were evaluated using PROCHECK and protein-sol. AllergenFP v.1.0 server was used to predict immunotoxin sensitivity and mRNA stability was assessed by RNAfold. Finally, docking between immunotoxin and HER2 was performed using the ClusPro server.

The results of the analysis showed that the hybrid protein can be a protein with a stable secondary structure in solution and has a strong three-dimensional structure and also has a relatively stable structure mRNA and can bind to the HER2 receptor.

The results of the designed immunotoxin indicated a stable and soluble protein with the ability to bind optimally to HER2 receptors, which makes it a suitable immunotoxin candidate for use in the treatment of breast cancer, the assurance of which requires studies. And its study is in clinical phases.