Development of a high-capacity adenoviral system expressing the Azurin gene and evaluation of antitumor activity

• Grant number: 23/11322-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Principal Investigator: Rodrigo Esaki Tamura
• Grantee: Kayo Alexandre Souza da Cruz
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil
• Associated research grant: 19/15619-2 - Development of high capacity adenoviral system expressing antitumoral genes, AP.JP

Abstract

Microbial agents have been used to fight cancer for over 100 years. Bacteria are capable of inducing death or activating the immune system against tumor cells. Since its initial proposal by William Coley, different bacteria have been used, including Streptococcus, Clostridium and the successful use of the bacillus Calmette-Guérin (BCG) from Mycobacterium bovis to treat bladder cancer. But not only inactivated bacteria have been used, the expression or direct inoculation of bacterial proteins or peptides has also been used to fight cancer. Among these, toxins, enzymes and specific metabolic products have also demonstrated the ability to induce death or direct the immune system against tumor cells. The Azurin antigen from Pseudomonas aeruginosa has demonstrated the ability to enter and induce the death of specifically tumor cells and not normal cells. Peptides derived from this protein have also demonstrated this same ability and are being analyzed in clinical trials for different forms of cancer. Among men, prostate cancer has the highest incidence, and metastatic forms are of enormous clinical relevance. The development of new treatments, such as gene therapy, have emerged and are increasingly being used to combat cancer. Among the most widely used vectors is the adenoviral vector, which is capable of transferring a therapeutic transgene of interest; for example, bacterial antigens such as Azurin, which is capable of specifically inducing the death of tumor cells. This project aims to develop a system using an adenoviral vector expressing the Azurin gene and to carry out tests on prostate cancer cells in order to evaluate the antitumor potential of Azurin in vitro and in vivo.