کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10798115 | 1053296 | 2005 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The novel chelator lipid 3(nitrilotriacetic acid)-ditetradecylamine (NTA3-DTDA) promotes stable binding of His-tagged proteins to liposomal membranes: Potent anti-tumor responses induced by simultaneously targeting antigen, cytokine and costimulatory sign
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کلمات کلیدی
dMPCPMvPoPCPEG400dimyristoyl-phosphatidylcholineChelator lipidT cell - سلول تیCytokine - سیتوکینplasma membrane vesicle - غشای پلاسما vesiclePlasma membrane vesicles - غشای پلاسما vesiclesLiposome - لیپوزوم هاCostimulatory molecule - مولکول مولکولی CostimulatoryTumor vaccine - واکسن تومورpalmitoyl-oleoyl-phosphatidylcholine - پالمیتویل-اولئویل فسفاتیدیل کولین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Recent studies indicate that the chelator lipid nitrilotriacetic acid ditetradecylamine (NTA-DTDA) can be used to engraft T cell costimulatory molecules onto tumor cell membranes, potentially circumventing the need for genetic manipulation of the cells for development of cell- or membrane-based tumor vaccines. Here, we show that a related lipid 3(nitrilotriacetic acid)-ditetradecylamine (NTA3-DTDA, which has three NTA moieties in its headgroup instead of one) is several-fold more effective than NTA-DTDA at promoting stable His-tagged protein engraftment. IAsys biosensor studies show that binding of His-tagged B7.1 (B7.1-6H) to NTA3-DTDA-containing membranes, exhibit a faster on-rate and a slower off-rate, compared to membranes containing NTA-DTDA. Also, NTA3-DTDA-containing liposomes and plasma membrane vesicles (PMV) engrafted with B7.1-6H and CD40-6H exhibit greater binding to T cells, in vitro and in vivo. Engrafted NTA3-DTDA-containing PMV encapsulated cytokines such as IL-2, IL-12, GM-CSF and IFN-γ, allowing targeted delivery of both antigen and cytokine to T cells, and stimulation of antigen-specific T cell proliferation and cytotoxicity. Importantly, use of B7.1-CD40-engrafted PMV containing IL-2 and IL-12 as a vaccine in DBA/2J mice induced protection against challenge with syngeneic tumor cells (P815 mammary mastocytoma), and regression of established tumors. The results show that stable protein engraftment onto liposomal membranes using NTA3-DTDA can be used to simultaneously target associated antigen, costimulatory molecules and cytokines to T cells in vivo, inducing strong anti-tumor responses and immunotherapeutic effect.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes - Volume 1716, Issue 2, 15 October 2005, Pages 104-116
Journal: Biochimica et Biophysica Acta (BBA) - Biomembranes - Volume 1716, Issue 2, 15 October 2005, Pages 104-116
نویسندگان
Christina L. van Broekhoven, Joseph G. Altin,