OncoTherad® (MRB-CFI-1) Nanoimmunotherapy: A Promising Strategy to Treat Bacillus Calmette-Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer: Crosstalk among T-Cell CX3CR1, Immune Checkpoints, and the Toll-Like Receptor 4 Signaling Pathway.

This study assessed the safety and efficacy of OncoTherad® (MRB-CFI-1) nanoimmunotherapy for non-muscle invasive bladder cancer (NMIBC) patients unresponsive to Bacillus Calmette-Guérin (BCG) and explored its mechanisms of action in a bladder cancer microenvironment.

A single-arm phase I/II study was conducted with 44 patients with NMIBC who were unresponsive to BCG treatment. Primary outcomes were pathological complete response (pCR) and relapse-free survival (RFS). Secondary outcomes comprised response duration and therapy safety. Patients' mean age was 65 years; 59.1% of them were refractory, 31.8% relapsed, and 9.1% were intolerant to BCG. Moreover, the pCR rate after 24 months reached 72.7% (95% CI), whereas the mean RFS reached 21.4 months. Mean response duration in the pCR group was 14.3 months. No patient developed muscle-invasive or metastatic disease during treatment. Treatment-related adverse events occurred in 77.3% of patients, mostly grade 1-2 events. OncoTherad® activated the innate immune system through toll-like receptor 4, leading to increased interferon signaling. This activation played a crucial role in activating CX3CR1+ CD8 T cells, decreasing immune checkpoint molecules, and reversing immunosuppression in the bladder microenvironment. OncoTherad® has proved to be a safe and effective therapeutic option for patients with BCG-unresponsive NMIBC, besides showing likely advantages in tumor relapse prevention processes.

International journal of molecular sciences. 2023 Dec 15*** epublish ***

João Carlos Cardoso Alonso, Bianca Ribeiro de Souza, Ianny Brum Reis, Gabriela Cardoso de Arruda Camargo, Gabriela de Oliveira, Maria Izabel de Barros Frazão Salmazo, Juliana Mattoso Gonçalves, José Ronaldo de Castro Roston, Paulo Henrique Ferreira Caria, André da Silva Santos, Leandro Luiz Lopes de Freitas, Athanase Billis, Nelson Durán, Wagner José Fávaro

Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), Universidade Estadual de Campinas (UNICAMP), Campinas 13083-865, São Paulo, Brazil., Obstetrics & Gynecology Department, Ovarian Cancer Research Group University of British Columbia, Vancouver, BC V6Z 2K8, Canada., Diagnosis and Surgery Department, Dentistry School, São Paulo State University (UNESP), Araraquara 14801-903, São Paulo, Brazil., Pathology Department, Medical School, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-888, São Paulo, Brazil.

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