Use of IL-17D for the treatment and prevention of cancers
Patent Number: US9205131
Executive Summary:
General Description:
Antitumor immunity suppresses cancer development. Using an unbiased global expression analysis approach, the inventor identifies a single gene — IL-17D — as sufficient and necessary for the rejection of some MCA sarcoma cell lines. IL-17D recruits NK cells via the induction of MCP-1 in tumor endothelial cells, leading to the generation and accumulation of M1 macrophages and priming of adaptive immune responses. The invention identifies a previously unappreciated mechanism of IL-17D in tumor surveillance and tumor rejection.
Scientific Progress:
Nuclear factor NRF-2 has been shown to induce IL-17D expression (refs. 3 and 4).
Future Directions:
Patent Status:
Publications:
1: Seelige R, Washington A Jr, Bui JD. The ancient cytokine IL-17D is regulated by Nrf2 and mediates tumor and virus surveillance. Cytokine. 2017 Mar;91:10-12. doi: 10.1016/j.cyto.2016.11.017. Epub 2016 Dec 9. PubMed PMID: 27940089; PubMed Central PMCID: PMC5316352.
2: Saddawi-Konefka R, Seelige R, Gross ET, Levy E, Searles SC, Washington A Jr, Santosa EK, Liu B, O'Sullivan TE, Harismendy O, Bui JD. Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance. Cell Rep. 2016 Aug 30;16(9):2348-58. doi: 10.1016/j.celrep.2016.07.075. Epub 2016 Aug 18. PubMed PMID: 27545889; PubMed Central PMCID: PMC5007173.
3: Saddawi-Konefka R, O'Sullivan T, Gross ET, Washington A Jr, Bui JD. Tumor-expressed IL-17D recruits NK cells to reject tumors. Oncoimmunology. 2015 Jan 7;3(12):e954853. eCollection 2014 Dec. PubMed PMID: 25964859; PubMed Central PMCID: PMC4353093.
4: O'Sullivan T, Saddawi-Konefka R, Gross E, Tran M, Mayfield SP, Ikeda H, Bui JD. Interleukin-17D mediates tumor rejection through recruitment of natural killer cells. Cell Rep. 2014 May 22;7(4):989-98. doi: 10.1016/j.celrep.2014.03.073. Epub 2014 May 1. PubMed PMID: 24794441; PubMed Central PMCID: PMC4084720.
Inventor Bio: Jack Bui
http://pathology.ucsd.edu/faculty/bui.htm
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Granted, Active
- Patent Link: https://patents.google.com/patent/US9205131/
- Research Institute: University of California, San Diego
- Disease Focus: Cancer
- Basis of Invention: Cytokine IL-17D is active in reducing, inhibiting, preventing and/or delaying the growth or proliferation of cancer cells and/or tumors
- How it works: IL-17D delivered to the tumor site recruits natural killer (NK) cells that polarize M1 macrophages in the tumor microenvironment. Thus, the tumor stops growing and shrinks
- Lead Challenge Inventor: Jack Bui
- Development Stage: Pre-clinical – mouse data
- Novelty:
- Use of IL-17D as tumor suppressor
- Use of IL-17D as tumor suppressor
- Clinical Applications:
- Topical, systemic, or gene monotherapy
- Combination with chemotherapy or immunotherapy
- Topical, systemic, or gene monotherapy
General Description:
Antitumor immunity suppresses cancer development. Using an unbiased global expression analysis approach, the inventor identifies a single gene — IL-17D — as sufficient and necessary for the rejection of some MCA sarcoma cell lines. IL-17D recruits NK cells via the induction of MCP-1 in tumor endothelial cells, leading to the generation and accumulation of M1 macrophages and priming of adaptive immune responses. The invention identifies a previously unappreciated mechanism of IL-17D in tumor surveillance and tumor rejection.
Scientific Progress:
Nuclear factor NRF-2 has been shown to induce IL-17D expression (refs. 3 and 4).
Future Directions:
- Phase I clinical trials
Patent Status:
- Filing date: 2012-03-30
- Publication date and Grant date: 2015-12-08
- Other versions: US20140086868A1 (Application)
Publications:
1: Seelige R, Washington A Jr, Bui JD. The ancient cytokine IL-17D is regulated by Nrf2 and mediates tumor and virus surveillance. Cytokine. 2017 Mar;91:10-12. doi: 10.1016/j.cyto.2016.11.017. Epub 2016 Dec 9. PubMed PMID: 27940089; PubMed Central PMCID: PMC5316352.
2: Saddawi-Konefka R, Seelige R, Gross ET, Levy E, Searles SC, Washington A Jr, Santosa EK, Liu B, O'Sullivan TE, Harismendy O, Bui JD. Nrf2 Induces IL-17D to Mediate Tumor and Virus Surveillance. Cell Rep. 2016 Aug 30;16(9):2348-58. doi: 10.1016/j.celrep.2016.07.075. Epub 2016 Aug 18. PubMed PMID: 27545889; PubMed Central PMCID: PMC5007173.
3: Saddawi-Konefka R, O'Sullivan T, Gross ET, Washington A Jr, Bui JD. Tumor-expressed IL-17D recruits NK cells to reject tumors. Oncoimmunology. 2015 Jan 7;3(12):e954853. eCollection 2014 Dec. PubMed PMID: 25964859; PubMed Central PMCID: PMC4353093.
4: O'Sullivan T, Saddawi-Konefka R, Gross E, Tran M, Mayfield SP, Ikeda H, Bui JD. Interleukin-17D mediates tumor rejection through recruitment of natural killer cells. Cell Rep. 2014 May 22;7(4):989-98. doi: 10.1016/j.celrep.2014.03.073. Epub 2014 May 1. PubMed PMID: 24794441; PubMed Central PMCID: PMC4084720.
Inventor Bio: Jack Bui
http://pathology.ucsd.edu/faculty/bui.htm
