Skip to main content

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.

Publication ,  Journal Article
Larchian, WA; Horiguchi, Y; Nair, SK; Fair, WR; Heston, WD; Gilboa, E
Published in: Clin Cancer Res
July 2000

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/10(6) 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 10(4) MBT-2 cells implanted orthotopically on day 0. Multiple vaccination schedules were performed with i.p. injection of 5 x 10(6) 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.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

July 2000

Volume

6

Issue

7

Start / End Page

2913 / 2920

Location

United States

Related Subject Headings

  • Urinary Bladder Neoplasms
  • Tumor Cells, Cultured
  • Transfection
  • T-Lymphocytes, Cytotoxic
  • Recombinant Proteins
  • Quaternary Ammonium Compounds
  • Phosphatidylethanolamines
  • Oncology & Carcinogenesis
  • Mice, Inbred C3H
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Larchian, W. A., Horiguchi, Y., Nair, S. K., Fair, W. R., Heston, W. D., & Gilboa, E. (2000). 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. Clin Cancer Res, 6(7), 2913–2920.
Larchian, W. A., Y. Horiguchi, S. K. Nair, W. R. Fair, W. D. Heston, and E. Gilboa. “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.Clin Cancer Res 6, no. 7 (July 2000): 2913–20.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

July 2000

Volume

6

Issue

7

Start / End Page

2913 / 2920

Location

United States

Related Subject Headings

  • Urinary Bladder Neoplasms
  • Tumor Cells, Cultured
  • Transfection
  • T-Lymphocytes, Cytotoxic
  • Recombinant Proteins
  • Quaternary Ammonium Compounds
  • Phosphatidylethanolamines
  • Oncology & Carcinogenesis
  • Mice, Inbred C3H
  • Mice