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Mixed Pancreatic Cancer Cell Lines Lysate-pulsed Human Dendritic Cell Vaccines Induce A Specific Antitumoral T CellResponse In Vitro

Posted on:2015-05-28Degree:MasterType:Thesis
Country:ChinaCandidate:J WangFull Text:PDF
GTID:2334330461958357Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
[Background and Objectives] Pancreatic cancer is a common malignancy with a dismal prognosis. Currently available treatments include surgical resection, chemotherapy, and radiotherapy. For those patients who undergo resection or chemotherapy, which demonstrated improvements in disease free survival and overall survival rates, new therapeutic approaches are still urgently needed. Immunotherapy for pancreatic cancer is expected to become one of the key treatments for this intractable disease. Our earlier experiments have proved the efficacy of anti-tumor of autologous mixed lymphocyte primed by BCG-activated DCs based Panc-1 lysate. My study is aimed to investigate the the anti-tumor effect induced by mixed pancreatic cancer cell lines lysate-pulsed human dendritic cell vaccines.[Methods] DCs were generated from peripheral blood through Ficoll-Hypaque gradient centrifugation, which were then stimulated with GM-CSF and IL-4 to induce differentiation. The DCs' phenotype and their secreting cytokines of IL-12 and TNF-? were measured following stimulating by tumor cell lysate and BCG Autologous mixed lymphocyte proliferation primed by activated DCs and the cytotoxicity of CTLs to pancreatic cancer cell line was measured by CCK-8 assay.[Results] We successfully got DCs from PBMC after stimulating by GM-CSF and IL-4. The expression of co-stimulatory molecules (CD80 and CD86) and the secreting cytokines of IL-12 and TNF-? was increased significantly after activated by mixed pancreatic cancer cell lines lysate when compared with single pancreatic cancer cell line lysate-pulsed mature DCs,. Mixed pancreatic cancer cell lines lysate-pulsed dendritic cells vaccines can stimulate autologous lymphocyte proliferation more efficiently, and CTLs showed a specific antitumoral T cell response in vitro. However, after stimulating by multiple pancreatic cancer cell lines lysate, a large number of dead DCs were observed.[Conclusion] DC vaccines against pancreatic cancer can be more maturated after activated by mixed pancreatic cancer cell lines lysate, and mixed pancreatic cancer cell lines lysate-pulsed dendritic cell vaccines can induce a specific antitumoral T cell response in vitro.
Keywords/Search Tags:Lysate, dendritic cells, pancreatic cancer, DC vaccines
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