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- Title
- Determining differential effects of Interleukin-2 on innate and adaptive immune cells in lymphoid organs and the gastrointestinal Tract.
- Creator
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Singh, Ayushi, McKinstry, Karl, Naser, Saleh, Copik, Alicja, University of Central Florida
- Abstract / Description
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Interleukin-2 (IL-2) is a pleiotropic cytokine demonstrated to be effective in treating cancer. However, the clinical use of IL-2 can be associated with severe side effects including gastrointestinal toxicity (GT). Similar GT symptoms are observed in inflammatory diseases such as CD (CD). Interestingly mounting evidence indicates a role for IL-2 in CD, but the underlying mechanisms are unknown. Indeed, studies on the in-vivo activities of IL-2 have mostly focused on secondary lymphoid organs...
Show moreInterleukin-2 (IL-2) is a pleiotropic cytokine demonstrated to be effective in treating cancer. However, the clinical use of IL-2 can be associated with severe side effects including gastrointestinal toxicity (GT). Similar GT symptoms are observed in inflammatory diseases such as CD (CD). Interestingly mounting evidence indicates a role for IL-2 in CD, but the underlying mechanisms are unknown. Indeed, studies on the in-vivo activities of IL-2 have mostly focused on secondary lymphoid organs and immune cells associated with them. Very few studies have addressed how IL-2 signals impact populations of immune cells in the gut. Here, we aim to identify and compare the effects of systemic IL-2 administration on six major leukocyte population and their subsets in mice using multicolor flow cytometry. While we confirmed previously observed changes in specific immune cell populations in the spleen, very few changes were seen in the gut and gut associated lymphoid tissues. Unexpectedly, a sharp decline was seen in B cells, most notably in Peyer's Patches, in mice treated with IL-2. Our data furthermore indicates that B cells in IL-2 treated mice undergo enhanced apoptosis in Peyer's Patches. Some studies suggest that changes in B cells may contribute to development of CD. Thus, this study may aid in defining ways in which IL-2 can contribute to disease etiology, and lead to novel treatments for CD.
Show less - Date Issued
- 2019
- Identifier
- CFE0007865, ucf:52777
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFE0007865
- Title
- THE EFFECT OF K562-IL21-2 PLASMA MEMBRANE PARTICLES ON THE PROLIFERATION OF NATURAL KILLER CELLS TO FIGHT CANCER.
- Creator
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Prophete, Michelle, Copik, Alicja, University of Central Florida
- Abstract / Description
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Immunotherapy has emerged as a current and future paradigm of cancer treatment, which utilizes the body's immune system to eradicate cancer. Natural Killer (NK) cells as part of the innate immune system have immense potential in their anti-tumor cytotoxic activities and host cell surveillance properties. NK cells comprise approximately five to fifteen percent of peripheral blood lymphocytes and can be proliferated in vitro using recently developed methods with co-cultures with feeder cells ...
Show moreImmunotherapy has emerged as a current and future paradigm of cancer treatment, which utilizes the body's immune system to eradicate cancer. Natural Killer (NK) cells as part of the innate immune system have immense potential in their anti-tumor cytotoxic activities and host cell surveillance properties. NK cells comprise approximately five to fifteen percent of peripheral blood lymphocytes and can be proliferated in vitro using recently developed methods with co-cultures with feeder cells (derived from engineered tumor cells) or plasma membrane (PM) particles, produced from the fore mentioned feeder cells, in combination with soluble cytokines. For efficient growth and maintenance of these NK cells, Interleukin-2 (IL-2) is utilized. IL-2 in solution, through receptor mediated signaling, stimulates proliferation of T-cells and NK cells. NK cells have lower responsiveness to IL-2 and consequently require a larger systemic dose to stimulate them as opposed to competing cell populations that have higher expression of receptors for IL-2, such as T-cells, which can have the effect of lower effective stimulation of NK cell growth. Such difference in the stimulatory capability of IL-2 toward NK cells and the short circulation lifetime of soluble IL-2 require higher dosages of soluble IL-2 for effective in vivo NK cell proliferation for therapeutic application against cancer, but is toxic. Therefore establishing another form of IL-2 delivery that improves its specific targeting to NK cells would be beneficial and may be crucial for novel therapeutic improvement. The Copik Laboratory has made an IL-2 fusion protein construct having a membrane anchor for expression of membrane-bound IL-2 on K562-41bbl-21 cells (K562-IL21). K562-IL21 cells are selectively recognized by NK cells and stimulate their proliferation and cytotoxicity. Hence, a K562-IL21 membrane-bound IL-2 form should be targeted to NK cells with IL-2 delivery. K562-IL21-2 cells were then used to prepare PM21-2 particles which have the potential to provide NK cell targeted, long-lived form of IL-2 for use as an injectable drug for in vivo adjuvant stimulation of NK cells. The presence of IL-2 on the in the PM21-2 particle product was verified by Western blot, and ELISA. Particle preparations from the modified K562 cells should possess characteristics that allow them to possibly replace soluble IL-2 and more specifically increase the numbers or anti-tumor activity of NK cell populations. The effect of PM21-2 particles was studied in in vitro culture based experiments, which tested the effectiveness the PM21-2 particles to induce selective NK cells expansion as compared to PM21 particles in the presence or absence of soluble IL-2.
Show less - Date Issued
- 2017
- Identifier
- CFH2000353, ucf:45918
- Format
- Document (PDF)
- PURL
- http://purl.flvc.org/ucf/fd/CFH2000353