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

• Tipo de documento: Artigo Científico
• Fonte: TISSUE & CELL; v. 93, p. 11-pg., 2025-02-11.

Resumo

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)

• Processo FAPESP: 22/09698-0 - Implicações Clínicas entre Resposta Imune, Checkpoints Imunológicos, Monoamina Oxidases e Proteínas HABP4 e SERBP1 no Câncer de Bexiga: Possíveis Biomarcadores Clínicos
• Beneficiário: Isadora Manzato Roberto
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/10052-1 - Novas Abordagens Terapêuticas para o Câncer de Bexiga Não-Músculo Invasivo (CBNMI): Uso Intravesical do Modificador de Resposta Biológica OncoTherad e Sua Associação com o Plasma Rico em Plaquetas (PRP)
• Beneficiário: Wagner José Fávaro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 23/15929-7 - Abordagem Terapêutica Emergente para o Câncer de Bexiga Não-Músculo Invasivo Mediante a Inibição da Monoamina Oxidase-A: Avaliação do Potencial Terapêutico do ImmunoClor
• Beneficiário: Wagner José Fávaro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 20/03419-6 - Efeitos terapêuticos e toxicológicos da imunoterapia com OncoTherad (MRB-CFI-1) em pacientes com câncer de bexiga não-músculo invasivo recidivado não responsivo à terapia com Bacillus Calmette-Guérin (BCG)
• Beneficiário: Wagner José Fávaro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/09699-6 - Crosstalk entre Células T CX3CR1+, Checkpoints Imunológicos e Monoamina Oxidases no Câncer de Bexiga Não-Músculo Invasivo: Implicações Clínicas da Nano-imunoterapia OncoTherad (MRB-CFI-1)
• Beneficiário: Monaliza Ávila
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 22/15126-9 - Duas famílias de proteínas reguladoras do ciclo celular: de estudos funcionais e uso como novos marcadores diagnósticos e alvos terapêuticos em câncer
• Beneficiário: Jörg Kobarg
• Modalidade de apoio: Auxílio à Pesquisa - Temático