Gmcsf and Ifnα gene therapy improves the response to BCG immunotherapy in a murine model of bladder cancer

To develop a strategy to improve response to bacillus Calmette-Gueri (BCG) using cytokine gene therapy ( + ). MB49-PSA tumor-bearing C57BL/6N mice were assigned into four groups: control; + therapy; BCG therapy or combined therapy ( + and BCG). In schedule 1, cytokine gene therapy was delivered befo...

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Veröffentlicht in:Future oncology (London, England) England), 2020-06, Vol.16 (17), p.1179-1188
Hauptverfasser: Tham, Sin Mun, Mahendran, Ratha, Chiong, Edmund, Wu, Qing Hui, Esuvaranathan, Kesavan
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container_issue 17
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container_title Future oncology (London, England)
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creator Tham, Sin Mun
Mahendran, Ratha
Chiong, Edmund
Wu, Qing Hui
Esuvaranathan, Kesavan
description To develop a strategy to improve response to bacillus Calmette-Gueri (BCG) using cytokine gene therapy ( + ). MB49-PSA tumor-bearing C57BL/6N mice were assigned into four groups: control; + therapy; BCG therapy or combined therapy ( + and BCG). In schedule 1, cytokine gene therapy was delivered before BCG therapy (eight instillations). In schedule 2, cytokine gene and BCG therapy were instilled alternatively (eight instillations). Tumors were analyzed by immunohistochemistry and mRNA analysis and urinary immune cells by flow cytometry. Combined therapy in schedule 2 reduced tumor growth, increased immune cell recruitment and was associated with reduced inflammation when compared with BCG therapy. Alternating cytokine gene delivery with BCG therapy modulates the tumor environment increasing receptivity to BCG.
doi_str_mv 10.2217/fon-2020-0137
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subjects Animals
Antigens
BCG Vaccine - therapeutic use
Biomarkers
Bladder cancer
Combined Modality Therapy
Cytokines
Cytokines - genetics
Disease Models, Animal
Female
Flow cytometry
Gene Expression
Gene therapy
Genetic Therapy - methods
Granulocyte-Macrophage Colony-Stimulating Factor - genetics
Histology
Immunomodulation - genetics
Immunotherapy
Interferon-alpha - genetics
Mice
Plasmids
Prostate
Schedules
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Transfection
Tumors
Urinary Bladder Neoplasms - diagnosis
Urinary Bladder Neoplasms - genetics
Urinary Bladder Neoplasms - immunology
Urinary Bladder Neoplasms - therapy
Variance analysis
Xenograft Model Antitumor Assays
title Gmcsf and Ifnα gene therapy improves the response to BCG immunotherapy in a murine model of bladder cancer
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