کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10901908 | 1084724 | 2015 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Enhanced anti-colon cancer immune responses with modified eEF2-derived peptides
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کلمات کلیدی
PBMCsmean fluorescence intensitiesPBSmAbGRBFITCMFICTLeEF2Granzyme BTCrOVAPBLsDMSO - DMSOE:T - E: TMonoclonal antibody - آنتی بادی مونوکلونالtumor-associated antigens - آنتی ژن های مرتبط با تومورOvalbumin - اوبلبومینadoptive immunotherapy - ایمونوتراپی پذیرفته شدهTransgenic - تراریختهTAAs - دوبارهDimethyl sulfoxide - دیمتیل سولفواکسیدColon cancer - سرطان کولونDendritic cell - سلول دندریتیکperipheral blood mononuclear cells - سلول های تک هسته ای خون محیطیfluorescence index - شاخص فلورسانسeukaryotic elongation factor-2 - ضریب کشش یوکاریوتی 2fluorescein isothiocyanate - فلوئورسین ایسوتیوسیاناتcytotoxic T lymphocyte - لنفوسیت T سیتوتوکسیکperipheral blood lymphocytes - لنفوسیت های خون محیطیPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریeffector:target - نمایشگر: هدفT cell receptor - گیرنده سلول T
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Eukaryotic elongation factor-2 (eEF2) is overexpressed in many human cancers and is an attractive target for cancer immunotherapy. The eEF2 derived polypeptides have been shown to be able to induce cytotoxic T lymphocytes from healthy donor. Here, we demonstrate the evidence indicating that modification of a segment of peptides from wild type eEF2-derived immunogenic peptides is able to further enhance its capacity of inducing antigen-specific cytotoxic T lymphocytes (CTLs) against colon cancer cells. Using peptide-MHC binding algorithms, potential HLA-A2.1-restricted epitopes capable of inducing specific CD8+ CTLs were identified. By analyzing HLA-A2.1 affinity and immunogenicity, we further identified one novel immunogenic peptide, P739-747 (RLMEPIYLV), that elicited specific CTL responses in HLA-A2.1/Kb transgenic mice and culture with peripheral blood lymphocytes from colon cancer patients. Furthermore, replacing certain amino acids (at positions 1, 3, 7) within the P739-747 sequence improved the immunogenicity against eEF2. Several analogs containing the auxiliary HLA-A*0201 anchor residues were able to stably bind to HLA-A*0201 and enhance CTL responses compared with the native sequence; two of them showed increased anti-tumor effects during the adoptive immunotherapy in vivo. Thus, these results support that modified immunogenic analogs are promising candidates for peptide-based cancer vaccination and immunotherapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 369, Issue 1, 1 December 2015, Pages 112-123
Journal: Cancer Letters - Volume 369, Issue 1, 1 December 2015, Pages 112-123
نویسندگان
Weihong Sun, Xiaofang Wei, Airong Niu, Xuezhen Ma, Jian Jian Li, Daiqing Gao,