OncoTherad® is an immunomodulator of biological response that downregulate RANK/RANKL signaling pathway and PD-1/PD-L1 immune checkpoint in non-muscle invasive bladder cancer

Abstract

Intoduction: Bladder cancer is the second most common urinary tract cancer. Above 70% of the occurrence of bladder cancer is superficial (pTis, pTa, and pT1), non-muscle invasive tumor (NMIBC), and the incidence of invasive disease is occasional. Treatments for NMIBC consist of transurethral resection (TUR) and subsequently intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), intending to prevent tumor progression and decrease recurrence. However, 20-30% of these tumors have progression, and 70% have a recurrence after exclusive TUR treatment. The immunomodulator of biological response, OncoTherad^®, is an attractive potential to revolutionize cancer therapy. In our previous studies with mice, the results showed that treatment with OncoTherad^® reduced 100% of tumor progression in NMIBC through the activation of Toll-Like Receptors' non-canonical pathway.

Materials and methods: In the present study, 36 female C57Bl/6J mice were divided into 6 groups (n = 6/group): Control, Cancer, Cancer + BCG, Cancer + OncoTherad^® (MRB-CFI-1), Cancer + P14-16 and Cancer + CFI-1. NMIBC was chemically induced and the treatments were followed for 6 weeks. A week after the last dose of treatment, animals were euthanized, the bladder was collected and routinely processed for immunohistochemical analyses of RANK, RANKL, FOXP3, and PD-1/PD-L1, such as PD-1/PD-L1 western blotting.

Conclusion: The immunohistochemical results showed that OncoTherad^® reduced RANK and RANKL immunoreactivities compared to the cancer group, which indicates a good prognosis. Immunohistochemical and western blotting analyses confirmed that OncoTherad^® modulated PD-1/PD-L1 immune checkpoint.

Keywords: Cancer treatment; FOXP3; Immune checkpoint; Immune system; RANKL.