Immunotherapy based on recombinant Bacillus Calmette-Guérin (BCG) for the treatment of bladder cancer in a murine model

• Grant number: 22/14764-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2023
• End date: February 29, 2024
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Ana Carolina Ramos Moreno
• Grantee: Daniela Delechiave
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 17/24832-6 - Development of vaccines based on recombinant BCG: Tuberculosis, Pertussis, Pneumococcus and Schistosoma, AP.TEM

Abstract

Bladder cancer is one of the top ten most common cancers in the world, accounting for 90% of all urothelial malignancies. Approximately 70% of bladder tumors are non-muscle invasive at diagnosis and are treated with transurethral resection followed by intravesical Bacillus Calmette-Guérin instillation (BCG). This bacterium is used in cancer adjuvant therapy to reduce recurrence and metastasis. To improve the adjuvanticity of BCG, we developed a recombinant BCG (rBCG) strain that expresses detoxified pertussis toxin S1 (rBCG-S1PT). Previously, we found that tumor-bearing mice treated with rBCG-S1PT lived longer than mice treated with native BCG. The purpose of this study is to investigate the anticancer effect of rBCG-S1PT in a preclinical model of heterotopic (subcutaneous) bladder cancer. We will investigate the profile of intratumoral, lymphoid organ, and systemic (blood) immune responses in mice treated with parental BCG vs rBCG to identify whether protective immunity is elicited by the vaccines and how it affects mice survival. Our findings will be useful in the translational research of our vaccine, which will have an impact on bladder cancer therapy.