Antitumor mechanisms of OncoTherad nano- immunotherapy involving toll-like 4 receptor-mediated signaling pathway, immune checkpoints and monoamine oxidases: clinical implications in bladder cancer

• Grant number: 22/04796-3
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): September 01, 2022
• Effective date (End): February 29, 2024
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Wagner José Fávaro
• Grantee: Gabriela Cardoso de Arruda Camargo
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Bacillus Calmette-Guerin (BCG) immunotherapy is the most effective form of intravesical therapy for the prophylaxis of recurrence and progression of non-muscle invasive bladder cancer (NMIBC). However, BCG immunotherapy is often associated with local and/or systemic adverse effects, including sepsis, in addition to tumor recurrence in up to 40% of cases. The incidence of these effects is significantly reduced with the use of chemotherapeutic agents. However, the response to intravesical chemotherapy is incomplete and tumor recurrence is high. Despite this, to date, there is no other therapy more effective than BCG on the market. In both Brazil and USA, the manufacture and distribution of BCG suffers from constant interruptions, which can negatively impact the treatment of patients with bladder cancer. Without this treatment, such patients have a high risk of tumor recurrence and progression. The surgical option, partial or total cystectomy, is often associated with high morbidity and mortality rates. Also, for some patients, cystectomy is not an available option due to the presence of comorbidities. Thus, new treatment modalities for patients with high-grade NMIBC, for whom BCG therapy has failed or is contraindicated, are increasing due to the development of new drugs. Immunotherapy has become a promising cancer therapy, improving the prognosis of patients with different types of cancers, and offering the possibility of long-term disease remission. Since NMIBC is sensitive to immunotherapy, immunomodulators that act as agonists of the immune system are considered promising candidates for the development of more effective treatments for NMIBC, without the accompanying side effects. In this scenario, a new perspective is represented by the OncoTherad® nanoimmunotherapy. OncoTherad® is a nanostructured inorganic phosphate complex associated with glycosidic protein (MRB-CFI-1), developed by the University of Campinas/Brazil, which has immunomodulatory and antitumor properties. This project is a prospective study that aims to evaluate the therapeutic and immunological effects of OncoTherad® nanoimmunotherapy in patients with NIMBC unresponsive to BCG (refractory, relapsed or intolerant) and/or intravesical chemotherapy, as well as to verify the cellular mechanisms triggered by this therapy. (AU)