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

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 resectio...

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Veröffentlicht in:Journal of cancer research and clinical oncology 2023-07, Vol.149 (8), p.5025-5036
Hauptverfasser: Reis, Ianny Brum, Tibo, Luiz Henrique Soares, de Souza, Bianca Ribeiro, Durán, Nelson, Fávaro, Wagner José
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Sprache:eng
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Zusammenfassung: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.
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-022-04449-5