In Vivo Study of Multi Potential Antigen in Generation of Dendritic Cell Vaccines
- سال انتشار: 1397
- محل انتشار: سومین جشنواره ملی و کنگره بین المللی علوم و فناوری های سلول های بنیادی و پزشکی بازساختی
- کد COI اختصاصی: NSCMRMED03_158
- زبان مقاله: انگلیسی
- تعداد مشاهده: 391
نویسندگان
Basic and Molecular Epidemiology of Gastrointestinal Disorder Research Center, Research Institute for Gastroenterology andLiver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran
Basic and Molecular Epidemiology of Gastrointestinal Disorder Research Center, Research Institute for Gastroenterology andLiver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran
Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Basic and Molecular Epidemiology of Gastrointestinal Disorder Research Center, Research Institute for Gastroenterology andLiver Diseases, Shahid Beheshti University of Medical Science, Tehran, Iran
چکیده
Background and Aim: One of the most effective approaches for cancertreating is the excitation of the immune system against tumor antigens.One of the strategies to stimulate T cell effectors and memory immuneresponse in cancer patients is to develop dendritic cell based vaccines.Microarray study indicated, LY6E is a common over expressed biomarkerin three GI cancers, colon, gastric, and pancreatic. The current researchpurpose is in vivo study of investigation the effectiveness of adoptingdendritic cells loaded with designed LY6E peptide antigen stimulating theMHC class I and II at the same time.Methods: LY6E was chosen according the differential gene expressionanalysis. In the next step, Immune Epitope Database and AnalysisResource (IEDB) was used as a prediction tool for MHC class I and class IIbinding site and design of epitopes. After that mononuclear cells extractedfrom murine bone marrow were cultured in conventional cytokines. Onday 7, cells were harvested and pulsed with peptide and subsequently,they were utilized for the maturation stage with LPS. DC phenotypesand characteristic were approved by flow cytometry (MHC Class II,CD80, CD40, CD14, and CD11c). Murine CT26 cell line were injectedsubcutaneously into Balb/c mice to create tumor and matured DCs pulsedwith peptides were injected into mice. 17 days after injection, mice weresacrificed and samples were collected. Proliferation, stimulation assays,Flow cytometry, and pathology detection were carried out to confirm theefficiency of LY6E peptide.Results: According to cytotoxicity assay (annexin/PI) extractedspelenocytes had a necrotic effect on CT26 as a cancer cell line. Regardingto tumor size, out of five treated mice, two of them showed significantamelioration. Flow cytometry analysis as another assessment, identifiedthe proliferation of CD8 positive cells as cytotoxic T lymphocytes inthe treated group. Following this, pathology samples indicated the G2grade in treated group where the untreated group had G3 and G4 gradeaccording to the TNM staging system.Conclusion: Identification and development of common tumor antigensprovide the possibility of immediate availability of DC vaccine. Theseanti-genes can provide more populations of cancer patients with availabletreatments. Finding a key player among the gastrointestinal cancers wasthe main concern of this study, therefore, by immunoinformatic approach;LY6E was detected as a core actor in three lethal GI malignancies (colon,Gastric, and pancreatic cancers). Our in vivo study characterized LY6E asa promising therapeutic candidate in GI cancers.کلیدواژه ها
Dendritic Cell; LY6E; GI cancer; Multi potential antigenمقالات مرتبط جدید
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