EVALUATION OF IMMUNOTHERAPY WITH ONCOTHERADÒ (MRB-CFI-1) FOR THE TREATMENT OF ORAL SQUAMOUS CELLS CARCINOMA IN RODENT MODEL

• Grant number: 23/08336-0
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Paulo Henrique Ferreira Caria
• Grantee: Paulo Henrique Ferreira Caria
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Gabriela de Oliveira ; Wagner José Fávaro

Abstract

Low survival rates in combination with significant toxicities caused by current treatment strategies used in oral squamous cell carcinoma (SCC) reinforce the urgent need for more effective therapeutic options. It has been widely accepted that the immune system plays a crucial role in cancer development, as tumor cells evade immunosurveillance by exploiting inhibitory checkpoint pathways that suppress antitumor T-cell responses. SCC has been intensively studied as an immunosuppressive disease. After the growing understanding of the mechanisms underlying the control of malignancies by the immune system, the establishment of immune therapies has emerged as a promising approach to the treatment of cancer. Given this scenario, our research group developed the OncoTherad® (MRB-CFI-1) immunotherapy, which has shown positive results in the treatment of different solid tumors. OncoTherad® (MRB-CFI-1) is a nanometric compound of phosphate and metallic salts associated with a glycosidic protein, capable of activating the innate immune system through signaling pathways mediated by toll-like receptors (TLR), triggering a response systemic acute inflammatory disease. Thus, the main objectives of the present study are to evaluate the therapeutic potential of the immunotherapy OncoTherad® (MRB-CFI-1) in the treatment of SCC-chemically induced in rats, as well as to investigate the possible mechanisms of action of this immunotherapy in the functioning of factors and signaling pathways interrelated and implicated in the complex microenvironment of SCC, constituting an informative panorama about the profile of the inflammatory/immune response to the treatment. Forty male Fischer 344 (F344/NTacUnib) rats with 80 days of age and average weight of 200g will be used. SCC will be induced on the left side of the lower lip of 20 rats by topical application of 9,10-dimethyl-1,2-benzanthracene (DMBA). One gram of DMBA will be diluted in 200 mL of acetone to obtain a 0.5% solution and applied every other day for 20 weeks. After the induction period, the animals will be divided into 04 groups (n=10 animals per group): Control Group: animals not induced to SCC will receive an intraoral dose of 0.3 mL of 0.9% saline solution, once per week for 6 consecutive weeks; Control Group+OncoTherad®: animals not induced to SCC will receive an intraoral dose of 0.3 mL of OncoTherad® (MRB-CFI-1; 20 mg/mL), once a week for 6 consecutive weeks; Cancer Group: animals induced to SCC will receive the same treatment as the animals in the Control Group; Cancer+OncoTherad® Group: animals induced to SCC will receive the same treatment as the Control+OncoTherad® Group. After the experimental period, the animals will be euthanized and the tumor lesions and normal oral tissue will be collected and submitted to macroscopic, histopathological, immunohistochemical and Western Blotting analyses. (AU)