New therapeutic perspective for non-muscle invasive bladder Cancer: use of the biological response modifier - inorganic phosphate complex 1 (MRB-CFI-1)

• Grant number: 17/04383-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2017
• Effective date (End): June 30, 2018
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Wagner José Fávaro
• Grantee: Melissa Sena da Silva
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Immunotherapy represents one of the approaches for the treatment of cancer. Compounds which are able to act as toll-like receptors (TLRs) agonists may represent promising candidates to be developed as medicines cancer. Nowadays, the most effective therapy to NMIBC is the Bacillus Calmette-Guerin (BCG) immunotherapy associated with transurethral resection (TUR). However, BCG causes side effects of different intensities from irritative symptoms to serious systemic reaction, which contributes to treatment interruption besides increasing cancer index recurrence after treatment, up to 30%. Based on this background, compounds activating the immune system, including biological response modifiers and tumor environment modulators are, considered potential candidates for the development of new NMBIC treatments aiming to obtain greater therapeutic effect combined with lower toxicity. Considering the importance of the development of drugs that can be administered intravesically and acting as agonists of TLRs, our research group developed a synthetic compound with antitumor and immunological properties called MRB-CFI-1 (Biological Response Modifier - Inorganic Phosphate Complex 1). Preliminary studies from our group demonstrated that MRB-CFI-1 led to significant tumor regression in rats chemically induced to CBNMI, indicating a significant antitumor effect of this compound involving the TLR4-mediated signaling pathway. Thus, the aims of this study are to characterize the histopathological and immunological effects of the MRB-CFI-1 compound and its components (CFI-1 and P14-16 protein) in the treatment of chemically induced CBNMI in rats, as well as to establish the possible mechanisms of action of this compound relating TLRs 2 and 4 with cell repair protein (p53). For NMIBC induction, 20 females rats Fisher 344 will receive N-methyl-N-nitrosourea (MNU) carcinogen, every other week for 8 weeks (a total of 4 doses). Five animals that will not receive MNU will be considered as Control group. Two weeks after the last dose of MNU, the animals will undergo ultrasound examination to evaluate tumor occurrence and then divided into 5 groups (5 animals per group): Control group; MNU Group (Cancer); MNU + Inorganic Phosphate Complex group; MNU + P14-16 protein; and MNU + MRB-CFI-1 group. It is expected to obtain more effective therapy with fewer side effects and that can supplement or replace traditional therapies such as BCG.