Dados do Trabalho

Título

ONCOTHERAD® IMMUNOTHERAPY DOWNREGULATED RANK/ RANKL SIGNALING PATHWAY IN NON-MUSCLE INVASIVE BLADDER CANCER

Introdução

Signaling between the receptor activator of nuclear factor-kB (RANK) and its ligand (RANKL) provides essential signals to modulating tumorigenesis. Also, RANK/RANKL inhibition may be an attractive approach to increase the effectiveness of immunotherapy. OncoTherad® immunotherapy stimulates immune system through Toll-like Receptors 2 and 4, resulting in an increased activation of the interferon signaling pathway, and represents a promising therapeutic perspective for non-muscle invasive bladder cancer (NMIBC).

Objetivo

This study characterized the therapeutic effects of OncoTherad® and its compounds (P14-16 protein and CFI-1) based on modulation of RANK/ RANK-L axis in an animal model of induced-NMIBC, as well as compared these effects with Bacillus Calmette-Guérin (BCG) treatment.

Método

Thirty-six female C57Bl/6J mice were divided into six groups (n=6): Control, Cancer, Cancer+BCG (40mg), Cancer+OncoTherad® (20 mg/ml), Cancer+P14-16 (20 mg/ml) and Cancer+CFI-1 (20 mg/ml). NMIBC was chemically induced (N-ethyl-N-nitrosourea 50mg/ml) and the treatments were followed for six weeks. Histopathological analyses were performed to evaluate the tumor progression comparing groups, such as immunohistochemical analyses (percentage of positive cells) of RANK/ RANKL axis.

Resultado

OncoTherad® and its compounds (CFI-1 and P14-16 protein) exhibited a robust antitumor response. The components CFI-1 and P14-16 both promoted 50% of tumor progression inhibition (TPI). OncoTherad® treatment showed better histopathological recovery of cancer state concerning its constituents and BCG, promoting 100% of TPI. The highest percentages of positive cells for RANK (p<0.05) were found in the Cancer (50.4%) and P14-16 (55.4%) groups as compared to the other experimental groups, showing moderate immunoreaction. OncoTherad® treatment was more effective in reducing RANK immunoreactivity (17.7%), showing weak immunoreaction concerning its compounds (P14-16 and CFI-1) and BCG and Cancer groups (p<0.01). Similarly, the lowest percentages of positive cells for RANKL were found in the OncoTherad® group (48.8%) compared to its compounds and BCG group. Although the results were not statistically significant, a decrease in RANKL immunoreactivity was observed after the P14-16 treatment.

Conclusão

The signaling of RANK/RANKL axis was significant in NMIBC immunology. OncoTherad® promoted downregulation in the RANK/ RANKL pathway in NMIBC, promoting inhibition of tumor progression.

Palavras-chave

Cancer treatment, Immunomodulator; Immune system.