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Purpose: Radionuclide gene therapy and immunotherapy have both been investigated as potential cancer treatments, but have been found to be ineffective as single therapies against aggressive tumors. In this study, I evaluated the tumoricidal effects of combined hMUC1 vaccination and hNIS radioiodine gene therapy in an animal tumor model. Experimental Design: A stable cell line (CT26/hMUC1-hNIS-Fluc: CMNF) expressing the hMUC1, hNIS, and Fluc genes was established using a retrovirus/lenti virus system. In vitro survival rates of CMNF cells were determined using I-131 (1 mCi) in vitro clonogenic assays. In addition, 1¡¿105 CMNF cells were transplanted into 28 mice, and 4 and 11 days after tumor challenge, tumor bearing mice were immunized intramuscularly with pcDNA (50§¶/50§¡) or pcDNA-hMUC1 (50§¶/50§¡), and subsequently injected with PBS (100§¡) or I-131 (2mCi/100§¡ in saline) intraperitoneally [4 groups (7 mice/group), which are referred to as the pcDNA+PBS, phMUC1+PBS, pcDNA+I-131, and phMUC1+I-131 groups]. Tumor progression was monitored using bioluminescence images and by taking caliper measurements. Tumor free mice (%) were defined as mice with no bioluminescence at tumor sites. Thirty-two days after the initial tumor challenge, mice in the pcDNA+I-131 and phMUC1+I-131 groups were rechallenged with CMNF cells (5¡¿104 cells/mouse). To investigate the hMUC1-associated immune response generated by combination therapy, the levels of hMUC1-associated CD8+IFN¥ã+T cells and hMUC1-associated CD8+IFN¥ã+T cells generated by hMUC1 antigen loaded CD11+ cells were examined. In addition, the cytotoxic effect of T cells on CMNF cells was measured using LDH assays. Results: FACS, I-125 uptake, and luciferase assays showed that CMNF cells highly expressed hMUC1, hNIS, and Fluc. In vitro clonogenic assays showed that the survival rates of CMNF cells were markedly reduced to 13.6 ¡¾ 1.0% compared with parental CT26 cells after treating them with 1 mCi of I-131. Marked tumor growth inhibition was only observed in the phMUC1+I-131 group by bioluminescence at 32 days after initial tumor challenge. In terms of long-term tumor protection, hMUC1-expressing cancer growth was completely inhibited in the phMUC1+I-131 group but not in the pcDNA+I-131 group after tumor re-challenge. Numbers of tumor free mice (%) were higher in the phMUC1+I-131 group than in the other three groups (pcDNA+PBS, phMUC1+PBS, pcDNA+I-131, and phMUC1+I-131, 0%, 0%, 14%, and 85%, respectively). Furthermore, levels of hMUC1-associated CD8+IFN¥ã+T cells were higher in the phMUC1+I-131 group than in the other three groups (pcDNA+PBS, phMUC1+PBS, pcDNA+I-131, and phMUC1+I-131 groups, 53.5¡¾1.2, 91.7¡¾1.7, 676.5¡¾3.6, and 1278.7¡¾3.4, respectively, P<0.02,). In addition, hMUC1-loaded CD11+cells in the phMUC1+I-131 group were found to be most effective at generating hMUC1-associated CD8+IFN¥ã+ T cells (pcDNA+PBS, phMUC1+PBS, pcDNA+I-131, and phMUC1+I-131, 7¡¾3, 31¡¾9, 86¡¾19, and 139¡¾15 cells, respectively, P<0.02,). Moreover, hMUC1-associated cytotoxic T cells (CTLs) activities against CMNF cell were higher in the phMUC1+I-131 group than in the other three groups (pcDNA+PBS, phMUC1+PBS, pcDNA+I-131, and phMUC1+I-131, 16¡¾2%, 20¡¾1%, 30¡¾2%, and 60¡¾2%, respectively, P<0.02). In the tumor rechallenge experiment, hMUC1-associated cytotoxic T cells (CTLs) activities against CMNF cells were higher in the phMUC1+I-131 group than in the pcDNA+I-131 group (96¡¾5% and 8¡¾2%, respectively, P<0.001). Conclusion: phMUC1 plus I-131 combination therapy generates more hMUC1associated immune response and synergistically induces a tumoricidal effect against hMUC1 expressing cancers. Furthermore, the results of the present study suggest that this combination therapy prevents tumor recurrence after complete remission has been achieved * Note: The text above is the abstract of the thesis. You can use the full-text by clicking the "Link" (URL) of item record and the viewer program will be installed automatically. In case of having problem with the viewer program installation, please download it manually using this url http://pdfdrm.snu.ac.kr/snudrm/download/PDFReaderSetup.exe