Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with <i>GMCSF+IFN α </i> Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model
This study evaluates a short therapy schedule for bladder cancer using BCG Tokyo. BCG Tokyo was evaluated in vitro using bone marrow derived dendritic cells, neutrophils, RAW macrophages and the murine bladder cancer cell line, MB49PSA, and compared to other BCG strains. BCG Tokyo > BCG TICE at i...
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| Format: | Article |
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MDPI AG
2021-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/12/1766 |
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| author | Sin Mun Tham Juwita N. Rahmat Edmund Chiong Qinghui Wu Kesavan Esuvaranathan Ratha Mahendran |
| author_facet | Sin Mun Tham Juwita N. Rahmat Edmund Chiong Qinghui Wu Kesavan Esuvaranathan Ratha Mahendran |
| author_sort | Sin Mun Tham |
| collection | DOAJ |
| description | This study evaluates a short therapy schedule for bladder cancer using BCG Tokyo. BCG Tokyo was evaluated in vitro using bone marrow derived dendritic cells, neutrophils, RAW macrophages and the murine bladder cancer cell line, MB49PSA, and compared to other BCG strains. BCG Tokyo > BCG TICE at inducing cytokine production. In vivo, high dose (1 × 10<sup>7</sup> colony forming units (cfu)) and low dose (1 × 10<sup>6</sup> cfu) BCG Tokyo with and without cytokine genes (<i>GMCSF + IFNα</i>) were evaluated in C57BL/6J mice (<i>n</i> = 12–16 per group) with orthotopically implanted MB49PSA cells. Mice were treated with four instillations of cytokine gene therapy and BCG therapy. Both high dose BCG alone and low dose BCG combined with cytokine gene therapy were similarly effective. In the second part the responsive groups, mice (<i>n</i> = 27) were monitored by urinary PSA analysis for a further 7 weeks after therapy cessation. More mice were cured at day 84 than at day 42 confirming activation of the immune system. Cured mice resisted the re-challenge with subcutaneous tumors unlike naïve, age matched mice. Antigen specific T cells recognizing BCG, HY and PSA were identified. Thus, fewer intravesical instillations, with high dose BCG Tokyo or low dose BCG Tokyo with <i>GMCSF + IFNα</i> gene therapy, can induce effective systemic immunity. |
| first_indexed | 2024-03-10T04:33:47Z |
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| id | doaj.art-7960192348184b8bb089ba4a19e5c84c |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T04:33:47Z |
| publishDate | 2021-11-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-7960192348184b8bb089ba4a19e5c84c2023-11-23T03:55:15ZengMDPI AGBiomedicines2227-90592021-11-01912176610.3390/biomedicines9121766Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with <i>GMCSF+IFN α </i> Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer ModelSin Mun Tham0Juwita N. Rahmat1Edmund Chiong2Qinghui Wu3Kesavan Esuvaranathan4Ratha Mahendran5Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 8, 1E Kent Ridge Road, Singapore 119228, SingaporeDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 8, 1E Kent Ridge Road, Singapore 119228, SingaporeDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 8, 1E Kent Ridge Road, Singapore 119228, SingaporeDepartment of Urology, National University Hospital, National University Health System, Singapore 119228, SingaporeDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 8, 1E Kent Ridge Road, Singapore 119228, SingaporeDepartment of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 8, 1E Kent Ridge Road, Singapore 119228, SingaporeThis study evaluates a short therapy schedule for bladder cancer using BCG Tokyo. BCG Tokyo was evaluated in vitro using bone marrow derived dendritic cells, neutrophils, RAW macrophages and the murine bladder cancer cell line, MB49PSA, and compared to other BCG strains. BCG Tokyo > BCG TICE at inducing cytokine production. In vivo, high dose (1 × 10<sup>7</sup> colony forming units (cfu)) and low dose (1 × 10<sup>6</sup> cfu) BCG Tokyo with and without cytokine genes (<i>GMCSF + IFNα</i>) were evaluated in C57BL/6J mice (<i>n</i> = 12–16 per group) with orthotopically implanted MB49PSA cells. Mice were treated with four instillations of cytokine gene therapy and BCG therapy. Both high dose BCG alone and low dose BCG combined with cytokine gene therapy were similarly effective. In the second part the responsive groups, mice (<i>n</i> = 27) were monitored by urinary PSA analysis for a further 7 weeks after therapy cessation. More mice were cured at day 84 than at day 42 confirming activation of the immune system. Cured mice resisted the re-challenge with subcutaneous tumors unlike naïve, age matched mice. Antigen specific T cells recognizing BCG, HY and PSA were identified. Thus, fewer intravesical instillations, with high dose BCG Tokyo or low dose BCG Tokyo with <i>GMCSF + IFNα</i> gene therapy, can induce effective systemic immunity.https://www.mdpi.com/2227-9059/9/12/1766BCG Tokyocombination of gene therapy and BCGbladder cancerantigen specific T cellssystemic immunity |
| spellingShingle | Sin Mun Tham Juwita N. Rahmat Edmund Chiong Qinghui Wu Kesavan Esuvaranathan Ratha Mahendran Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with <i>GMCSF+IFN α </i> Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model Biomedicines BCG Tokyo combination of gene therapy and BCG bladder cancer antigen specific T cells systemic immunity |
| title | Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with <i>GMCSF+IFN α </i> Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model |
| title_full | Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with <i>GMCSF+IFN α </i> Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model |
| title_fullStr | Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with <i>GMCSF+IFN α </i> Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model |
| title_full_unstemmed | Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with <i>GMCSF+IFN α </i> Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model |
| title_short | Intravesical High Dose BCG Tokyo and Low Dose BCG Tokyo with <i>GMCSF+IFN α </i> Induce Systemic Immunity in a Murine Orthotopic Bladder Cancer Model |
| title_sort | intravesical high dose bcg tokyo and low dose bcg tokyo with i gmcsf ifn α i induce systemic immunity in a murine orthotopic bladder cancer model |
| topic | BCG Tokyo combination of gene therapy and BCG bladder cancer antigen specific T cells systemic immunity |
| url | https://www.mdpi.com/2227-9059/9/12/1766 |
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