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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)

Funder: São Paulo Research Foundation

Funding period
0
Funding amount
Abstract
Bladder cancer (BC) is the second most common malignant disease of the urinary tract, and one of the most costly neoplasms for the Unified Health System. The primary treatment of non-muscle invasive bladder cancer (NMIBC) is based on transurethral resection, followed by intravesical immunotherapy with Bacillus Calmette-Guérin (BCG), to decrease recurrence and prevent tumor progression. However, the use of BCG is associated with side effects of varying intensities, ranging from mild irritative symptoms to severe systemic reaction, which contributes to treatment discontinuation and has a post-treatment recurrence rate of up to 30%. In this way, the development of new therapies for the treatment of CBNMI, which are more effective and present less adverse effects than the classic therapies, are very relevant. Considering the importance of the development of drugs that can be administered intravesically and acting as modulators of the immune system, our research group developed a synthetic nanostructured compound with antitumor and immunological properties called OncoTherad (MRB-CFI-1 - Biological Response Modifier - Inorganic Phosphate Complex 1). Our group demonstrated that in the treatment of chemically induced CBNMI in mice, OncoTherad led to significant tumor regression, indicating a significant antitumor effect of this compound involving the interferon signaling pathway for Toll-like receptors (TLRs) 2 and 4-mediated. In addition, the use of phosphate moieties can exert a number of biological activities, since polyphosphates (PolyP) are secreted by activated platelets and mast cells, interfering in coagulation and innate immune response. Considering the importance of the modulation of the receptors of the immune system by these phosphate species and their relation with activated platelets, our research group investigated the importance of Platelet Rich Plasma (PRP) in the modulation of these receptors and demonstrated that PRP was able to exert antitumor effects mediated by the immune system. Thus, the main objectives of this study will be to characterize the histopathological and molecular effects of the OncoTherad nanostructured complex associated with PRP in the treatment of CBNMI chemically induced in mice, as well as to establish the possible mechanisms of action of this therapeutic association involving the TLRs 2 and 4 signaling pathways, STAT/ JAK1/JAK2 and RANK/ RANKL/ OPG cell signaling pathways, PDGF/ IGF-1/ TGF-² growth factors, and PD-1/ PD-L1 immune checkpoint pathway. (AU)

 
56
Projects
USD 25.3 M
Aggregated funding amount
USD 575 K
Average funding amount
Project list item
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

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Project list item
[Efficacy and toxicity of bladder instillation of anti-tumor peptide for inhibition of bladder tumor in mice] - Original in Japanese

Japan Society for the Promotion of Science to Toru SHIMAZUI, Takahiro KOJIMA, Hiroyuki NISHIYAMA, Kazuhiro YOSHIKAWA

USD 39,492
2019 - 2022
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Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 372,404
2019 - 2021
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Phase 1/2 Study of Modern Immunotherapy in BCG-Relapsing Urothelial Carcinoma of the Bladder - (ADAPT-BLADDER)

National Cancer Institute to NOAH M HAHN

USD 1,313,632
2019 - 2024
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Identifying DNA Biomarkers of Bacillus Calmette-Guerin (BCG) Resistance in Non-Muscle-Invasive Bladder Cancer

Canadian Institutes of Health Research to Jack Victor Warren Bacon, Alexander William Wyatt

USD 847
2018 - 2019
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Novel recombinant BCG for immunotherapy of bladder cancer

National Cancer Institute to BORIS SHOR

USD 290,014
2018 - 2020
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Transurethral En Bloc Versus Standard Resection of Bladder Tumour: A Multi-centre Randomised Controlled Trial (EB-StaR study).

University Grants Committee to TEOH Yuen Chun Jeremy

USD 75,486
2018 - 2020
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Intra-operative MRI-guided Robotic System for Photothermal Therapy of Bladder Cancer

University Grants Committee to Kwok Ka Wai, Wong Kenneth Kin Yip, Vardhanabhuti Varut Vince, TEOH Yuen Chun Jeremy

USD 81,014
2018 - 2021
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Deciphering the neoantigen landscape in bladder cancer patients

Swiss National Science Foundation to Laurent Derré, Sylvain Nguyen, Alexandre Harari

USD 642,703
2018 - 2022
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Ty21a immunotherapy of non-muscle-invasive bladder cancer

Swiss National Science Foundation to Denise Nardelli Haefliger, Lenka Chalupova, Patrice Jichlinski, Mathieu Chevalier

USD 437,441
2018 - 2021
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INTRAVESICAL ONCOLYTIC THERAPY FOR BLADDER CANCER

National Cancer Institute to ROSA MARIA DIAZ, LUKKANA SUKSANPAISAN, BRADLEY C. LEIBOVICH

USD 1,990,950
2017 - 2020
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[The development of new BCG Immunotherapy against bladder cancer with immune checkpoint inhibitor] - Original in Japanese

Japan Society for the Promotion of Science to ARIO TAKEUCHI

USD 42,460
2017 - 2020
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Investigation of Genetic and Immune Mechanisms of Response to BCG for Non-Muscle Invasive Bladder Cancer: A Translational Study of S1602

Congressionally Directed Medical Research Programs to David Mcconkey

USD 437,139
2016 - 2017
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Investigation of Genetic and Immune Mechanisms of Response to BCG for Non-Muscle Invasive Bladder Cancer: A Translational Study of S1602

Congressionally Directed Medical Research Programs to Joshua J Meeks

USD 661,890
2016 - 2017
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Investigation of Genetic and Immune Mechanisms of Response to BCG for Non-Muscle Invasive Bladder Cancer: A Translational Study of S1602

Congressionally Directed Medical Research Programs to Robert Svatek

USD 428,545
2016 - 2017
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Role of antigen-specific immunity in BCG therapy for bladder cancer

Bladder Cancer Advocacy Network to Niannian Ji, Robert Scott Svatek

USD 50,000
2016 - 2018
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Visible Light-Controlled Combination Strategy for Treating Nonmuscle Invasive Bladder Cancers

Congressionally Directed Medical Research Programs to Kelly Standifer

USD 592,000
2015 - 2016
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