Chronic Myeloid Leukemia Dendritic Cell Vaccine Mediated By The Specific Anti-leukemia Effect

Chronic myeloid leukemia is a clonal myeloproliferative disorder of the hematopoietic stem cell. The curitive measures are still deficiency.With regard to tumor therapy, more and more people play focus on adjusting auto-immunity or exploring operative immune components to eliminate tumor. A lot of clinical and laboratory evidences show that CML cells have immumogenicity and can provide an attractive tumor target for vaccination. In recent 10 years, tumor specific T cells were separated from CML patients, however, they are anergy to tumor and failure to initiate tumor specific responses because of the quantity and function of antigen presenting cells(APCs). The efficency of antigen by professional antigen-presenting cells is crucial to the induction of positive T-help and cytotoxic T-cell responses. The most potent APCs are dendritic cells. They can present antigen efficiently to memory T cells and initiate immune responses in native T cells, they play an important role in antitumor, antiinfection, autoimmune and transplantation immunity. They are far more efficient than other presenting cells, such as B cells and macrophages. DCs can express many immune correlation molecules, such as MHC-Ⅰ, MHC-Ⅱ, B7 and ICAM-1 highly and by the production of cytokines such as interleukine 12(IL-12) that direct TH1 cell differenation and elite primary and secondary antitumor immune responses in vivo and in vitro. They are the hot spot in the domain of tumor research and very important in the tumor immunetherapy.The development of techniques to generate tumor specific DCs in large numbers in vitro from peripheral blood monocytes or haempoietic progenitors has recently led to new approaches to cancer adoptive immunotherapy. In this thesis, we explore the feasibility of Dendritic cells (DCs) induced from chronic myeloid leukemia (CML) with different cytokine cocktails and the mechanisms of immunological response by specific T lymphocytes primed by this kind DC vaccine. Monocytes populations for the generation of DC were collected from patients with high numbers of circulating peripheral blood CML cells, then cultured with different cytokine cocktails. DCs were studied for morphology and immunofluorescent staining. RT-PCR was used to analyze the specific fusion genes of culture-derived DC and chromosome banding technique were used to detect Philadelphia chromosome (ph1). In vitro, DCs were used to induce auto-lymphocytes to be activated CTL and killing rates were assayed. T subgroups and IL-12 contents in the supernents were assayed also. After incubation, all these CML-derived cells developed typical DC morphology and the expression of DC-associated surface molecules upregulated, and ph1 positive cells decreased in the cytokine cocktails which contains IFN-α( p＜0.05＝. The contents of IL-12 in the co-culture system of CML-DC and lymphocytes increased and the activated lymphocytes skewed from Th1 to Th2, exhibiting more killing activities to auto- CML cells than K562 cell, HL60 and xeno-CML cells. The results of this research will supply new approach for specific immunotherapy of CML. The results of this research supply the application value for the CML derived DC vaccine against CML.