http://dx.doi.org/10.14288/1.0447290
department or school: Medicine, Faculty of
department or school: Non UBC
department or school: Obstetrics and Gynaecology, Department of
data provider: DSpace
identifier citation: International Journal of Molecular Sciences 24 (24): 17535 (2023)
contributor: Ovarian Cancer Research Centre (Vancouver, B.C.)
creator: Alonso, João Carlos Cardoso
creator: de Souza, Bianca Ribeiro
creator: Reis, Ianny Brum
creator: de Arruda Camargo, Gabriela Cardoso
creator: de Oliveira, Gabriela
creator: de Barros Frazão Salmazo, Maria Izabel
creator: Gonçalves, Juliana Mattoso
creator: de Castro Roston, José Ronaldo
creator: Caria, Paulo Henrique Ferreira
creator: da Silva Santos, André
creator: de Freitas, Leandro Luiz Lopes
creator: Billis, Athanase
creator: Durán, Nelson
creator: Fávaro, Wagner José
issued: 2024-11-19T22:15:39Z
issued: 2023-12-15
description: 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.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/89678
note: Citation: Alonso, J.C.C.; de Souza,B.R.; Reis, I.B.; de Arruda Camargo,G.C.; de Oliveira, G.; de BarrosFrazão Salmazo, M.I.; Gonçalves,J.M.; de Castro Roston, J.R.; Caria,P.H.F.; da Silva Santos, A.; et al.OncoTherad® (MRB-CFI-1)Nanoimmunotherapy: A PromisingStrategy to Treat Bacillus Calmette–Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer: Crosstalkamong T-Cell CX3CR1, ImmuneCheckpoints, and the Toll-LikeReceptor 4 Signaling Pathway. Int. J.Mol. Sci. 2023, 24, 17535. https://doi.org/10.3390/ijms242417535Academic Editor: Hideki FuruyaReceived: 8 November 2023Revised: 9 December 2023Accepted: 13 December 2023Published: 15 December 2023Copyright: © 2023 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). International Journal of Molecular SciencesArticleOncoTherad® (MRB-CFI-1) Nanoimmunotherapy: A PromisingStrategy to Treat Bacillus Calmette–Guérin-UnresponsiveNon-Muscle-Invasive Bladder Cancer: Crosstalk among T-CellCX3CR1, Immune Checkpoints, and the Toll-Like Receptor 4Signaling PathwayJoão Carlos Cardoso Alonso 1,2,*, Bianca Ribeiro de Souza 3 , Ianny Brum Reis 4 ,Gabriela Cardoso de Arruda Camargo 1, Gabriela de Oliveira 1, Maria Izabel de Barros Frazão Salmazo 1,Juliana Mattoso Gonçalves 1, José Ronaldo de Castro Roston 1, Paulo Henrique Ferreira Caria 1 ,André da Silva Santos 1, Leandro Luiz Lopes de Freitas 5, Athanase Billis 5, Nelson Durán 1and Wagner José Fávaro 1,*1 Laboratory of Urogenital Carcinogenesis and Immunotherapy (LCURGIN), Universidade Estadual deCampinas (UNICAMP), Campinas 13083-865, São Paulo, Brazil; gcacamargo0@gmail.com (G.C.d.A.C.);gabriela.ufscar@gmail.com (G.d.O.); mabelfrazao@hotmail.com (M.I.d.B.F.S.);jumattosogg@gmail.com (J.M.G.); rroston@uol.com.br (J.R.d.C.R.); phcaria@unicamp.br (P.H.F.C.);andre.s.s@me.com (A.d.S.S.); nelsonduran1942@gmail.com (N.D.…
has type: Article
is shown at: 10.14288/1.0447290
language: eng
peer review status: Reviewed
provider: Vancouver : University of British Columbia Library
publisher: Multidisciplinary Digital Publishing Institute
publisher DOI: 10.3390/ijms242417535
rights: CC BY 4.0
rights URI: https://creativecommons.org/licenses/by/4.0/
scholar level: Faculty
scholar level: Researcher
subject: bladder cancer
subject: immunotherapy
subject: Oncotherad
subject: bacillus Calmette–Guerin
subject: nanotechnology
title: 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
type: Text
identifier URI: http://hdl.handle.net/2429/89678