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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 29, 2017 |
| Title |
Genome-wide analysis of genes induced in TRAMP mouse prostate tumors after Mobilan injection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Toll-like receptor 5 is considered an attractive target for anticancer immunotherapy. TLR5 agonists, bacterial flagellin and engineered flagellin derivatives, have been shown to have potent anti-tumor and metastasis-suppressive effects in multiple animal models and to be safe in both animals and humans. Anticancer efficacy of TLR5 agonists stems from TLR5-dependent activation of NF-kB that mediates innate and adaptive anti-tumor immune responses. To extend application of TLR5-targeted anticancer immunotherapy to tumors that do not naturally express TLR5, we created an adenovirus-based vector for intratumor delivery, named Mobilan that drives expression of self-activating TLR5 signaling cassette comprising of human TLR5 and a secreted derivative of Salmonella flagellin structurally analogous to a clinical stage TLR5 agonist, entolimod. Co-expression of TLR5 receptor and agonist in Mobilan-infected cells established an autocrine/paracrine TLR5 signaling loop resulting in constitutive activation of NF-kB both in vitro and in vivo. Injection of Mobilan into primary tumors of the prostate cancer-prone TRAMP mice resulted in a strong induction of multiple genes involved in inflammatory responses and mobilization of innate immune cells into the tumors including neutrophils and NK cells and suppressed tumor progression. Intratumoral injection of Mobilan into subcutaneously-growing syngeneic prostate tumors in immunocompetent hosts improved animal survival after surgical resection of the tumors, by suppression of tumor metastasis. In addition, vaccination of mice with irradiated Mobilan-transduced prostate tumor cells protected mice against subsequent tumor challenge. These results provide proof-of-concept for Mobilan as a tool for antitumor vaccination that directs TLR5-mediated immune response towards cancer cells and does not require identification of tumor antigens.
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| Overall design |
Total RNA obtained from prostate tumors 24 and 48 hours after injection of PBS, Ad-mCherry or Mobilan (two replicates)
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| Contributor(s) |
Mett V, Gudkov A |
| Citation(s) |
28967901 |
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| Submission date |
Jul 28, 2017 |
| Last update date |
Feb 28, 2018 |
| Contact name |
Vadim Mett |
| E-mail(s) |
vmett@buffalobiolabs.com
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| Phone |
3025408705
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| Organization name |
Buffalo BioLabs, LLC
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| Street address |
73 High Street
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| City |
Buffalo |
| State/province |
NY |
| ZIP/Postal code |
14203 |
| Country |
USA |
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| Platforms (1) |
| GPL18752 |
Illumina MouseWG-6 v2.0 expression beadchip [gene symbol version] |
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| Samples (12)
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| GSM2722121 |
Ad-mCherry, 24h, tumor 2 |
| GSM2722122 |
M-VM3, 24h, tumor 1 |
| GSM2722123 |
M-VM3, 24h, tumor 2 |
| GSM2722124 |
PBS, 48h, tumor 1 |
| GSM2722125 |
PBS, 48h, tumor 2 |
| GSM2722126 |
Ad-mCherry, 48h, tumor 1 |
| GSM2722127 |
Ad-mCherry, 48h, tumor 2 |
| GSM2722128 |
M-VM3, 48h, tumor 1 |
| GSM2722129 |
M-VM3, 48h, tumor 2 |
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| Relations |
| BioProject |
PRJNA396227 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE102023_non-normalized_data.txt.gz |
5.8 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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