Clinical and immunohistochemical effects of OncoTherad (MRB-CFI-1) nanoimmunotherapy on SERBP1, HABP4, CD44 and Ki-67 in BCG-unresponsive non-muscle invasive bladder cancer

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Salmazo, Maria Izabel de Barros Fraza ; Alonso, Joao Carlos Cardoso ; Camargo, Gabriela Cardoso de Arruda ; de Oliveira, Gabriela ; Santos, Andre da Silva ; Avila, Monaliza ; Roberto, Isadora Manzato ; de Freitas, Leandro Luiz Lopes ; Bottene, Martim Correa ; Lestingi, Jean Felipe Prodocimo ; Caria, Paulo Henrique Ferreira ; Duran, Nelson ; Kobarg, Jorg ; Favaro, Wagner Jose

• Document type: Journal article
• Source: TISSUE & CELL; v. 93, p. 11-pg., 2025-02-11.

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-Gue<acute accent>rin (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 (MRBCFI-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. (AU)

• FAPESP's process: 22/09698-0 - Clinical Implications Among Immune Response, Immune Checkpoints, Monoamine Oxidases, HABP4 and SERBP1 Proteins in Bladder Cancer: Possible Clinical Biomarkers
• Grantee: Isadora Manzato Roberto
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/10052-1 - New Therapeutic Approaches for Non-Muscle Invasive Bladder Cancer (NMIBC): Intravesical Use of OncoTherad Biological Response Modifier and Its Association with Platelet Rich Plasma (PRP)
• Grantee: Wagner José Fávaro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 23/15929-7 - Emerging Therapeutic Approach for Non-Muscle Invasive Bladder Cancer through Monoamine Oxidase-A Inhibition: Assessment of the Therapeutic Potential of ImmunoClor
• Grantee: Wagner José Fávaro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/03419-6 - Therapeutic and toxicological effects of OncoTherad (MRB-CFI-1) immunotherapy in patients with BCG-refractory or relapsed non-muscle invasive bladder cancer
• Grantee: Wagner José Fávaro
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/09699-6 - Crosstalk Among T-Cells CX3CR1+, Immune Checkpoints and Monoamine Oxidases in Non-Muscle Invasive Bladder Cancer: Clinical Implications of OncoTherad Nano-Immunotherapy (MRB-CFI-1)
• Grantee: Monaliza Ávila
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/15126-9 - Two cell cycle regulatroy protein families: from functional studies to their use as novel diagnostic markers and therapeutic targets in cancer
• Grantee: Jörg Kobarg
• Support Opportunities: Research Projects - Thematic Grants