ZIABC011150 (ZIA) | |||
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Title | Chronic Inflammation and Carcinogenesis | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Durum, Scott | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $422,172 | Project Dates | 10/01/2008 - N/A |
Fiscal Year | 2012 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) Digestive Diseases (100.0%) Inflammatory Bowel Disease (100.0%) |
Colon/Rectum (100.0%) | ||
Research Type | |||
Cancer Initiation: Oncogenes and Tumor Suppressor Genes Localized Therapies - Discovery and Development |
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Abstract | |||
The new Cancer Inflammation Program has inspired two new projects in colon cancer that diverge from our previous focus on IL-7. One project involves IL-17A , IL-17 F and IL-25. These are T cell cytokines that are produced by cells that strongly promote the intestinal inflammation that leads to colon cancer. It has not been determined where IL-17 and 25 are produced during this inflammatory response. We have developed knockin reporter mice for the two IL-17 genes using two colors and for IL-25. This will enable us to visualize cells producing these critical inflammatory cytokines during bowel inflammation leading to colon cancer. A second project aims to inhibit the bowel inflammation leading to colon cancer. IL-27 and IL-35 are suppressive cytokines that we have cloned into the food bacterium, Lactococcus lactis. These engineered bacteria were given orally to mice with experimentally-induced fatal IBD. IL-27 rescued all mice from IBD and death and therefore is an extremely promising therapeutic. The mechanism appears to be through secondary induction of the suppressive cytokine IL-10, and subsequent inhibition of many inflammatory cytokines such as IL-23 and IL-6. We have now extended the L.lactis-IL-27 therapy to three very different mouse models of IBD, and potent therapeutic efficacy is seen in all three, greatly encouraging the development of a human trial. Currently we are characterizing a new L.lactis-IL-27 construct that is designed for human therapy. |