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

William A. Larchian, Yutaka Horiguchi, Smita K. Nair, William R. Fair, Warren D W Heston, Eli Gilboa

Research output: Contribution to journalArticle

26 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2913-2920
Number of pages8
JournalClinical Cancer Research
Volume6
Issue number7
StatePublished - Jul 1 2000
Externally publishedYes

Fingerprint

Urinary Bladder Neoplasms
Liposomes
Genetic Therapy
Interleukin-2
Vaccination
Transfection
Genes
Cancer Vaccines
Therapeutics
Neoplasms
Retroviridae
Carcinogens
Appointments and Schedules
Plasmids
Cytokines
Cell Line
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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. / Larchian, William A.; Horiguchi, Yutaka; Nair, Smita K.; Fair, William R.; Heston, Warren D W; Gilboa, Eli.

In: Clinical Cancer Research, Vol. 6, No. 7, 01.07.2000, p. 2913-2920.

Research output: Contribution to journalArticle

Larchian, William A. ; Horiguchi, Yutaka ; Nair, Smita K. ; Fair, William R. ; Heston, Warren D W ; Gilboa, Eli. / 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. In: Clinical Cancer Research. 2000 ; Vol. 6, No. 7. pp. 2913-2920.
@article{63bcb12abc20449da8d9de04b85718fb,
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.",
author = "Larchian, {William A.} and Yutaka Horiguchi and Nair, {Smita K.} and Fair, {William R.} and Heston, {Warren D W} and Eli Gilboa",
year = "2000",
month = "7",
day = "1",
language = "English",
volume = "6",
pages = "2913--2920",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "7",

}

TY - JOUR

T1 - Effectiveness of combined interleukin 2 and B7.1 vaccination strategy is dependent on the sequence and order

T2 - A liposome-mediated gene therapy treatment for bladder cancer

AU - Larchian, William A.

AU - Horiguchi, Yutaka

AU - Nair, Smita K.

AU - Fair, William R.

AU - Heston, Warren D W

AU - Gilboa, Eli

PY - 2000/7/1

Y1 - 2000/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033927218&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033927218&partnerID=8YFLogxK

M3 - Article

C2 - 10914741

AN - SCOPUS:0033927218

VL - 6

SP - 2913

EP - 2920

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 7

ER -