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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
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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)

 
39
Projects
USD 22.6 M
Aggregated funding amount
USD 666 K
Average funding amount
Project list item
Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 203,510
2019 - 2021
Project list item
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 656,816
2019 - 2024
Project list item
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 75,274
2018 - 2020
Project list item
Deciphering the neoantigen landscape in bladder cancer patients

Swiss National Science Foundation to Laurent Derré

USD 639,521
2018 - 2022
Project list item
Ty21a immunotherapy of non-muscle-invasive bladder cancer

Swiss National Science Foundation to Denise Nardelli Haefliger

USD 436,670
2018 - 2021
Project list item
CISTO: Comparison of Intravesical Therapy and Surgery as Treatment Options for Bladder Cancer

Patient-Centered Outcomes Research Institute to John Gore

USD 8,500,000
2018 - 2022
Project list item
INTRAVESICAL ONCOLYTIC THERAPY FOR BLADDER CANCER

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

USD 1,081,593
2017 - 2020
Project list item
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
Project list item
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
Project list item
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
Project list item
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
Project list item
Regulatory T cells in intravesical BCG therapy for non-muscle invasive bladder cancer

Japan Society for the Promotion of Science to Mitsuhiro NARITA, Eiki Hanada, 亮介 村井, Akihiro KAWAUCHI, Kazumasa OGASAWARA, Susumu KAGEYAMA, Tatsuhiro YOSHIKI

USD 45,237
2014 - 2017
Project list item
Ty21a Salmonella as immunotherapeutic agent against non-muscle-invasive bladder cancer

Swiss National Science Foundation to Denise Nardelli Haefliger

USD 387,838
2014 - 2017
Project list item
Mechanisms underlying dampening of the immune response in non-muscle invasive bladder cancer (NMIBC)

Swiss National Science Foundation to Laurent Derré, Patrice Jichlinski

USD 319,918
2013 - 2016
Project list item
Efficacy of BCG Therapy is a Function of Bladder Tumor Immune Microenvironment

National Cancer Institute to JAMES JOSEPH LEE

USD 391,738
2013 - 2015
Project list item
Development of bladder cancer immunotherapy

Canadian Cancer Society to Yves Fradet, Pedro De campos lima, Hélène Larue

USD 836,290
2013 - 2018
Project list item
Metabolomics in the prediction of recurrence and progression of non-muscle invasive bladder cancer

Swiss National Science Foundation to Malte Rieken

 
2013 - 2013
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