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The Experiment Study Of Anti-Liver Carcinoma By Tumor Vaccine Of Dendritic Cells

Posted on:2006-12-09Degree:MasterType:Thesis
Country:ChinaCandidate:J LvFull Text:PDF
GTID:2144360155952598Subject:Surgery
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The major treatment of malignance is operation, radiotherapy and chemotherapy. but all above-mentioned can,t prevent cancer from metastasis and recurrence, so can,t treate cancer thoroughgoing. during the process of treatment cancer, human explored and found some new method, these method were enhanced and perfected constantly in treatment of tumor. cancer vaccine is a new method of cancer treatment. the last few years, this method have acquired obviously effect in tumor treatment field. in this study, we will confer the type,action and effection of tumor vaccine in tumor treatment field. Tumor vaccine is a tumor antigen specific activated immunone (ASI), it is a new immunotherapy of cancer. It's principle is: by separate extract tumor specific antigen (TSA) or tumor associated antigen (TAA),fabricate different kinds of vaccine and inject it to tumor or patient, then antigen presenting cells (APC) ingest and render it to immune cells, make T cells aquired activity, produce tumor specific cytotoxic T lymphocyte cells (CTL), comvine and kill tumor cells in specifically. Tumor vaccine can classifed into follow types according tumor antigen: (1) tumor cell vaccine. (2) tumor protein antigen vaccine. (3) synthesize multiple-peptide vaccine. (4) anti-typical vaccine. (5) gene engineering vaccine. in this study, we will confer to use tumor heat shock protein (HSP) as antigen and dendritic cells (DC) as vector constitute dendritic cells tumor vaccine and exam it's fuction of kill tumor cells in vitro. DC was found in 1973 year by Steinman and Cohn, it is called because it can produce lot of things like branch in mature. DC has a strongly function, it can activate native T cell in vivo and it's function is unique. it is a professional antigen presenting cell (APC) also. it can activated CD8+ CTL and CD4+ Th cell, control process of immune reaction in vico. Heat shock protein (HSP) is a synthesize production when orgnism by a serial of injury signals challenged such as high temperature, poison and some heavy metals. according to the molecular weight of HSP, they can be divided into several families, such as HSP110, HSP90, HSP70, HSP60, low molecular weight of HSP and ubiquitin, and HSP70 is the main member in HSP family. HSPs have various functions. First, HSPs endowed cells and life-forms the ability to recover from the damages by stress factors and protect them against these damages, the most significant phenomenon is thermo-tolerance; Second, HSPs can protect genetic materials in cells and deliver main functions in the process of growth, development and differentiation. Third, HSPs have close interaction with a lot of important bioactivity factors such as steroids, cytokines and oncogenes, and take part in some regulation processes. Fourth, HSPs function as molecular chaperones. Chaperones are a kind of molecules, which mediate the interaction in proteins or among protein. During the process of depolymerization, degradation,formation of natural conformation of proteins, chaperones can bind and using buffers freshly prepared are the key steps. When tumor cells are growing and proliferating, some intracellular proteins will be degraded into fractions of peptides, parts of which are tumor specific antigens. As molecular chaperones, HSPs can bind these peptides and bear tumor specific antigens. Immunotherapy of mice by using the HSP70-peptide complex purified from autogenous tumor, not only can protect mice from the challenge of tumor cells, but also can regress the tumors already established. HSP-peptide complexes used as vaccine have some benefits: 1. Since HSPs-peptide complexes come from individual, it will not have any toxicity and side effects when it is injected back to the individual; 2. HSPs themselves can act as adjuvant and HSPs-peptide complexes as vaccine do not need any help from other kind of adjuvant; 3. HSP shave very high immune effect. 6ug HSP70-peptide complexes can protect mice from the challenge of tumor cells when HSP70-peptide complexes were used in mice; 4. HSPs-peptide complexes carrying all kinds of peptides in cells, they can avoid immune escape of tumor cells when used as vaccines. In this study, we selected umbilical cord blood as pre-dendritic cells, established a kind of method of induced DC by cord blood in vitro. and, we extracted HSP-peptide complex of Liver carcinoma cells, then combine DC with HSP-peptide complex in culture medium, make DC carried the HSP-peptide complex, determined anti-cancer activity of DC with HSP-peptide complex as well as DC...
Keywords/Search Tags:immunotherapy, tumor vaccine, dendritic cells, HSP-peptide complex, CTL activity
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