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Study On The Glycosyl-phosphatidylinositol-B7-1Anchored Into Renal Carcinoma Cell Membranes Enhancing CTL's Ability To Kill The Carcinoma Cells

Posted on:2008-09-30Degree:MasterType:Thesis
Country:ChinaCandidate:H X GeFull Text:PDF
GTID:2144360215989276Subject:Surgery
Abstract/Summary:PDF Full Text Request
Renal Cell Carcinoma (RCC) is a kind of immunogenicity tumor. T lymphocyteplays an important role in the anti-tumor immuno-reaction process. There are two signalsto make T lymphocyte activated. The one is T cell receptor (TCR)-MHC-I complex. Theother is T cell corresponding receptor connecting with costimulatory adhesion molecule.The RCC always lacks costimulatory molecule, so T cell can not be activated or inductedto apoptosis. This course is called immune escape.In the tumor immunity, B7-1 molecule is an important factor, but B7-1 molecule isnot expressed on RCC, then immune escape would be happened. In this study, wemodified RCC cell membranes with transferring costimulatory adhesion molecules B7-1,aiming to develop tumor immunotherapy for RCC. We certificated that protein transfer ofglycosyl-phosphatidylinositol(GPI) anchored costimulatory molecule into RCC cellmembranes, which can be used as an alternative to gene transfer for tumorimmunotherapy. Through this way, CD4+, CD8+ and NK can be activated and proliferateand the ability of anti-tumor is enhanced. The metastasis and the relapse of RCC will bedecreased.GPI-B7-1 was expressed by CHO/DHFR-cells transfected with pCDNA3 vectorencoding this chimeric protein and plasmid pSV2-dhfr was identified and analysised bydirect immunofluorescence. The fusion protein was isolated from the cell surface ofCHO/DHFR-by TX-100. Depurated GPI-B7-1 was able to re-anchore the RCC cellmembranes stably on suitable conditions. We cultured the autologous CTL admixed theRCC membranes anchored GPI-B7-1, then isolated the CTL and detected the functionof the CTL. By MTT, we investigated that CTL could be activated by the autologous RCC membrane GPI-B7-1 anchored. The ability of killing the RCC of the activatedCTL was improved conspicuously. We studied the significance of the tumor vaccineGPI-B7-1 anchored and perspective of the tumor vaccine GPI protein transferred intumor immunity.
Keywords/Search Tags:glycosyl-phosphatidylinositol(GPI), B7-1, CTL, tumor immunotherapy, RCC
PDF Full Text Request
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