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Study On Antitumor Effect Of Immunoactive Vector

Posted on:2001-07-16Degree:MasterType:Thesis
Country:ChinaCandidate:Y K WangFull Text:PDF
GTID:2144360002450917Subject:Internal medicine
Abstract/Summary:PDF Full Text Request
Object: Vaccine therapy for established metastases as wellas prophylactic effect to prevent outgrowth of latent metastatictumor cells would be beneficial in clinical. Our goal is toinvestigate an effective, specific, and convenient way in activeimmunotherapy of malignant tumors. We try to activate both CD4+ andCD8+ Tlymphocytes in order to completely eradicate ramnant tumorcells after surgery.Methods: BALB/c mice and MM45T. Li cell line (a tumor cell linederived from mouse liver cancer which can readily grow in BALB/cmouse) are used to establish model tumor. Tumor cells have beentransfected with syngeneic major histocompatibility complex classâ…¡ previously, and then tumor membrane protein adsorbed on theinactivated tumor cells'surface. Experiments were performed inthree groups of mice: mice in control group were inoculated wildtype tumor without any treatment, mice in treatment group werevaccinated after model metastic tumor had established, and micein protection group were vaccinated before high dosage of tumorcells inoculation. We observed whether there were or were not tumorgrowth and, if so, the tumor velocity. Furthermore, MTT assay wasused to determine the capacity of Tlymphocytes proliferationstimulation by tumor membrane protein in vitro. Dot Blot assay wasperformed as well to detect anti-tumor-protein antibodies in miceserum.Results: We found that the mice in both control and treatmentgroup were invaded by MM45T.li cells 12 days after inoculation.There were, however, no tumor occurred in mice in protection groupthroughout the who1e period of experiment. We a1 so observed tumorgrowth in treatment group decreased 4--8 weeks after immunizationcompared wi th those of control group. MTT assay showed the capaci tyof tumor membrane protein to st imulate T lymphocytes to pro1 iferate.Dot B1ot assay demonstrated specific ant ibodi es ari sen in protectedmice. Moreover, a 1ower antibody titer was detected in serum oftreated mi ce, yet there was no vi s ib1e Ag--Ab react ion between serumof control group mice and the tumor protein.Discussion: Vacc ines prepared wi th tumor ce l 1 s themselvesexpress ing MHC--I I mol ecules and membrane protein adsorbed on thesurface can improve the antigen quantities exposed to the immunitysystem, thus they are capab 1 e of act ivat ing CD4+Th as we 1 l as CD8+CTL.In vivo studies in mouse tumor models demonstrate that vaccinationcould protect against future cha1lenge wi th wi 1d--type tumor, reduceestabl ished metastatic disease, and extend mean surviva1 time. Invi tro studies showed both T cel l immuni ty and humoral immuni ty wereinduced. Adaptation of these vaccines for the treatment of humanmetastatic cancers wi11 be a wide1y app1ied strategy with highspecifici ty and efficacy in treating of human metastatic tumors.
Keywords/Search Tags:Tumor, Immunotherapy, Major Histocompatibility, Complex (MHC), Gene
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