Effectiveness of combined interleukin 2 and B7.1 vaccination strategy is dependent on the sequence and order: A liposome-mediated gene therapy treatment for bladder cancer Journal Article
| Authors: | Larchian, W. A.; Horiguchi, Y.; Nair, S. K.; Fair, W. R.; Heston, W. D. W.; Gilboa, E. |
| Article Title: | Effectiveness of combined interleukin 2 and B7.1 vaccination strategy is dependent on the sequence and order: A liposome-mediated gene therapy treatment for bladder cancer |
| Abstract: | We have developed a novel liposome-mediated immunogene therapy using interleukin 2 (IL-2) and B7.1 in a murine bladder cancer model. A carcinogen- induced murine bladder cancer cell line, MBT-2, was transfected with cationic liposome 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleolylphosphatidylethanolamine and IL-2 plasmid. The optimized transfection condition generated IL-2 levels of 245-305 ng/106 cells/24 h, 100-fold higher than the levels seen with retrovirus transfection. Ninety percent of the peak level of IL-2 production was maintained for up to 11 days after transfection. Animal studies were conducted in C3H/HeJ female mice with 2 x 104 MBT-2 cells implanted orthotopically on day 0. Multiple vaccination schedules were performed with i.p. injection of 5 x 106 IL-2 and/or B7.1 gene-modified cell preparations. The greatest impact on survival was observed with the day 5, 10, and 15 regimen. Control animals receiving retrovirally gene-modified MBT-2/IL-2 cell preparations had a median survival of 29 days. Animals receiving the IL-2 liposomally gene-modified cell preparation alone had a median survival of 46 days. Seventy-five percent of animals receiving IL-2 followed by B7.1 gene-modified tumor vaccines were the only group to show complete tumor-free survival at day 60. All of these surviving animals rejected the parental MBT-2 tumor rechallenge and survived at day 120 with a high CTL response. In conclusion, liposome-mediated transfection demonstrates a clear advantage as compared with the retroviral system in the MBT-2 model. Multi-agent as opposed to single-agent cytokine gene-modified tumor vaccines were beneficial. These 'targeted' sequential vaccinations using IL-2 followed by B7.1 gene-modified tumor cells significantly increased a systemic immune response that translated into increased survival. |
| Keywords: | cancer survival; treatment outcome; disease-free survival; drug efficacy; nonhuman; combined modality therapy; animal cell; mouse; animals; mice; interleukin 2; drug administration schedule; animal model; tumor cells, cultured; transfection; bladder cancer; urinary bladder neoplasms; immune response; genetic transfection; cancer vaccines; recombinant proteins; vaccination; t-lymphocytes, cytotoxic; plasmid; gene therapy; cytokine production; lipids; phosphatidylethanolamines; liposome; liposomes; drug carriers; interleukin-2; mice, inbred c3h; antigens, cd80; quaternary ammonium compounds; adeno associated virus; female; priority journal; article; ammonium derivative; glycerophospholipids |
| Journal Title: | Clinical Cancer Research |
| Volume: | 6 |
| Issue: | 7 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2000-07-01 |
| Start Page: | 2913 |
| End Page: | 2920 |
| Language: | English |
| PUBMED: | 10914741 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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