Agradecimentos: This research was funded by the São Paulo Research Council (FAPESP grant numbers: 2018/10052-1; 2020/03419-6; 2022/15126-9; 2022/09699-6; 2022/09698-0; 2023/15929-7), and the Brazilian National Council for Scienti?c and Technological Development (CNPq grant numbers: 552120/2011-1; 312396/2021-0) Ver menos

Abstract: Non-muscle-invasive bladder cancer (NMIBC) is a malignancy with a high recurrence and progression rate, particularly in patients who fail to respond to standard Bacillus Calmette-Guérin (BCG) therapy. OncoTherad (MRB-CFI-1) nanoimmunotherapy has emerged as a promising therapeutic option, with potential to modulate immune responses and inhibit tumor progression. This study evaluated the clinical efficacy of OncoTherad (MRB-CFI-1) nanoimmunotherapy in patients with BCG-unresponsive NMIBC and investigated correlations between therapeutic outcomes and histopathological and molecular findings. In this retrospective cross-sectional study, 20 patients with BCG-unresponsive NMIBC were treated with OncoTherad (MRB-CFI-1) across two clinical centers. Bladder tissue samples were collected before and after treatment, and immunohistochemical analyses were performed to assess the expression of SERBP1, HABP4, CD44, and Ki-67. Primary endpoints included pathological complete response (pCR), recurrence-free survival (RFS), and duration of response (DoR), which were analyzed in relation to immunohistochemical biomarker findings. Our results demonstrated that high Ki-67 proliferative index and elevated immunoreactivity for CD44 and SERBP1 were associated with shorter RFS. Treatment with OncoTherad (MRB-CFI-1) significantly reduced (p < 0.05) the immunoreactivity of SERBP1 and CD44, which was accompanied by a marked decrease in Ki-67 proliferative index, indicating effective suppression of tumor activity. Conversely, a significant increase (p < 0.05) in HABP4 immunoreactivity was observed, suggesting a protective role against NMIBC recurrence and progression. A pCR was achieved in 65 % of patients, with a median RFS of 21.1 months and a median DoR of 15.7 months, underscoring the clinical efficacy of OncoTherad (MRB-CFI-1). These findings suggest that OncoTherad (MRB-CFI-1) nanoimmunotherapy offers a novel and effective treatment strategy for patients with BCG-unresponsive NMIBC, providing a promising alternative to radical cystectomy and significantly improving patient outcomes Ver menos