Assessment of IL-18 gene expression using Salmonella typhimurium in the control of colorectal cancer cells in vitro and in vivo.

• Grant number: 22/06194-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2023
• Status: Discontinued
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Fernanda de Freitas Anibal
• Grantee: Talita Motta Quiarim
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated scholarship(s): 24/01808-6 - Modified Salmonella Typhimurium with IL-18 gene as treatment option for aggressive and metastatic colorectal cancer: Assessing the therapeutic potential in a metastatic CRC organoid mouse model and human colorectal cancer organoids, BE.EP.DR

Abstract

Cancer is defined as a group of malignant diseases characterized for its uncontrolled growth of anormal cells. Colorectal cancer represents the third most common cancer in the world, and it leads the worldwide mortality rate. It is a cancer that has a low growth and can become metastatic leading 86% of the patients to death. The conventional treatments have limitations in the fight against cancer due to limited penetration into cancer cells. With the advance in immunotherapy studies, which is a therapy that stimulates the immune system to fight against cancer cells, it has become evident the role of bacterias that helps in the transportation of therapeutical agents inside cancer cells leading to the reduction of the tumour and increasing the patient survival. IL-18 is a cytokine tumour-specific that has the ability to eliminate cancer cells and recent studies shows that has a protection role in colorectal adenocarcinomas, becoming a potential candidate to a therapeutical agent in immunotherapies. This study plans to assess the activity of therapeutic agents using IL-18 genes in expression models with Salmonella typhimurium to control cancer cells growth in colorectal cancer in vitro and in vivo. With HCT-8 cancer cells, it will be assessed the antitumoral action of IL-18 in vitro and it will be inserted into modified Salmonella typhimurium (SL3621), it will also be performed in vivo assays using mouse models to evaluate the biodistribution of the therapeutical agents and the cytotoxic effects in the tumour control. It is expected to obtain positive results with the decrease in tumour growth and increase in animal survival, evidencing the efficacy of this kind of immunotherapy in colorectal cancer.