| ` Chronic myelogeous leukemia (CML) is a clonal disorder of a pluripotent hematopietic stem cell associated in over 95%of cases with the Ph chromosome. This cytogenetic abonormality results from a reciprocal translocation involving chromosome 9 band q34 and chromosome 22 band q11,forming a fusion gene on chromosome 22 from the protonco gene ABL and the BCR gene, both expressed in normal cells and encoding presumably nonimmmunogenic proteins. High –dose chemoradiotherapy and autologous bone marrow transplantation can induce transient remission in patients with CML. Both normal and malignant progenitors are present in this disease. Relapse after auotologous bone marrow transplantation is related to the presence of malignant cells in the marrow graft, which can probably be eliminated by cytotoxic immune therapy. Products of either the b3a2or b2a2 exon junction with abnormal tyrosine kinase activity, at the fusion point, of a codon or an amino acid not derived from either the bcr or abl proteins, which provide the potent specific antigen to T lymphocyte cell. However, CML cells don't express co-stimulatory molecules, which makes T cell anergy.Dendritic cells (DCs) are the most powerful professional antigen-presenting cells (APC) specialized in the initiation of primary immune responses.. They possess an exceptional capability to capture antigens, process and present antigenic peptide fragments, express lymphocyte co-stimulatory molecules, migrate to lymphoid organs and secrete cytokines to induce primary immune responses of both CD8+ and CD4+ T cells. Now data concerning cancer immune therapy have been shown to be capable of inducing a specific antitumor response in vitro and in vivo. Some clinical experiments are in their I stage and II stage ,such as mutiple myeloma, melaoma.Interleukin –18 (IL-18) is found to be an important immune regulatory cytokines in recent years. With many biological functions, including the ability to induce IFN-γ,augment the cytotoxic activity of NK and CTL cells, promoting proliferation of T cells and cytotoxic activity by Fas. IL-18 is an antitumor cytokine which has good applying prospect. Dendritic cells(DC) capable of improving proliferation and priming T cell., induing high levels of IL-12 and Th1 immune reaction . DC can also induce antigen-specific CTL and enhance specific kill tumors. Moreover Il-18 and IL-12 synergistially upregulate the production of IFN-γ by Th1 cells and improve immune reaction . In conclusion , combing IL-18 and DC can augment antitumor effect.In the study leukemia dendritic cells were induced from CML peripheral blood and the morphological, phenotypic properties and function of DC were determined .We detected whether Dc can effectively present antigen and na?ve T cell inducing specific effect of kill tumors. Then dendritic cells were vaccinate for patients with CML and the therapy effect were observed which will establish the basis for future clinical application. In order to study the effect of IL-18 on CML therapy, CML-DC were transfected with pVAX1-IL-18 plasmid .The effects of CML-DC transfected IL-18 on the specific CTL and NK were detected.. This will provide a method for improving antitumor effect .The research of CML vaccinated with DC has not been reported in our country. It is the first report of antileukemia effect by IL-18 transfected CML-DC .1. The study on dendritic cells derived from CML cells in vitro and antileukemia immune response activated by dendritic cells. In this study, we induced DCs from CML peripheral blood mononuclear cells by GM-CSF,TNF-(,IL-4 . In addition, the cells were detected for morphological and phenotypic properties by inversed microscope, electro- microscope and FACS. DC exhibited the typical morphology with thin cytoplasmatic process , Transmission electron microscopy revealed that the cell surface had many irregular dendrities, numerous mitochondria, but scanty lysosomes, ribosomes. and expressed high levels of HLA-DR,CD80,CD86,CD1a.CML cells incubated concurrently with |
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