Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer

J. Vieweg, D. Boczkowski, K. M. Roberson, D. W. Edwards, M. Philip, R. Philip, T. Rudoll, C. Smith, C. Robertson, Eli Gilboa

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

We have shown previously that treatment of rats bearing the Dunning R3327 MatLyLu prostatic tumor with human interleukin 2 (IL-2) gene-modified tumor cell preparations induces potent antitumor immunity in the animal. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of prostate cancer, we have explored the use of a simplified gene delivery system based on liposomes to introduce and express the IL-2 gene in the Dunning rat R3327 MatLyLu prostatic tumor cell line (MatLyLu) and in short-term cultures of primary human prostatic tumor cells. Liposome-DNA complexes containing the adenoassociated virus inverted terminal repeats exhibited 3-10-fold higher levels of gene transfer and IL-2 expression than did liposome complexes with non-adeno-associated virus containing plasmids. Single transfections resulted in IL-2 expression for an extended period of time that exceeded severalfold the amount of IL-2 secreted from retrovirally transduced MatLyLu cells. X-irradiation of cells (4000 rads) prior to transfection did not affect cytokine secretion, indicating that liposome- mediated gene transfer dues nut depend un cell proliferation. High levels of gene transfer and IL-2 expression were also achieved in short-term cultures of primary human prostatic tumor cells established from tumor specimens obtained following radical prostatectomy of cancer patients. Depending on the type of liposome used, IL-2 levels secreted from the human prostatic tumor cells were comparable to or exceeded the levels of IL-2 secreted from retrovirally transduced MatLyLu cells, which induced antitumor immunity in the rat model. The ability to culture and expand ex vivo human prostatic tumor cells, and the use of a simple and highly efficient gene transfer method to generate genetically modified tumor vaccines, set the stage for clinical exploration of gene-based immunotherapy of prostate cancer.

Original languageEnglish
Pages (from-to)2366-2372
Number of pages7
JournalCancer Research
Volume55
Issue number11
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Dependovirus
Liposomes
Genetic Therapy
Interleukin-2
Prostatic Neoplasms
Plasmids
Genes
Neoplasms
Cancer Vaccines
Transfection
Immunity
Satellite Viruses
Gene Transfer Techniques
Nuts
Terminal Repeat Sequences
Prostatectomy
Tumor Cell Line
Immunotherapy
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Vieweg, J., Boczkowski, D., Roberson, K. M., Edwards, D. W., Philip, M., Philip, R., ... Gilboa, E. (1995). Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer. Cancer Research, 55(11), 2366-2372.

Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer. / Vieweg, J.; Boczkowski, D.; Roberson, K. M.; Edwards, D. W.; Philip, M.; Philip, R.; Rudoll, T.; Smith, C.; Robertson, C.; Gilboa, Eli.

In: Cancer Research, Vol. 55, No. 11, 01.01.1995, p. 2366-2372.

Research output: Contribution to journalArticle

Vieweg, J, Boczkowski, D, Roberson, KM, Edwards, DW, Philip, M, Philip, R, Rudoll, T, Smith, C, Robertson, C & Gilboa, E 1995, 'Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer', Cancer Research, vol. 55, no. 11, pp. 2366-2372.
Vieweg J, Boczkowski D, Roberson KM, Edwards DW, Philip M, Philip R et al. Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer. Cancer Research. 1995 Jan 1;55(11):2366-2372.
Vieweg, J. ; Boczkowski, D. ; Roberson, K. M. ; Edwards, D. W. ; Philip, M. ; Philip, R. ; Rudoll, T. ; Smith, C. ; Robertson, C. ; Gilboa, Eli. / Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer. In: Cancer Research. 1995 ; Vol. 55, No. 11. pp. 2366-2372.
@article{1fda1c337db34377ad285ffe1a5cb513,
title = "Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer",
abstract = "We have shown previously that treatment of rats bearing the Dunning R3327 MatLyLu prostatic tumor with human interleukin 2 (IL-2) gene-modified tumor cell preparations induces potent antitumor immunity in the animal. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of prostate cancer, we have explored the use of a simplified gene delivery system based on liposomes to introduce and express the IL-2 gene in the Dunning rat R3327 MatLyLu prostatic tumor cell line (MatLyLu) and in short-term cultures of primary human prostatic tumor cells. Liposome-DNA complexes containing the adenoassociated virus inverted terminal repeats exhibited 3-10-fold higher levels of gene transfer and IL-2 expression than did liposome complexes with non-adeno-associated virus containing plasmids. Single transfections resulted in IL-2 expression for an extended period of time that exceeded severalfold the amount of IL-2 secreted from retrovirally transduced MatLyLu cells. X-irradiation of cells (4000 rads) prior to transfection did not affect cytokine secretion, indicating that liposome- mediated gene transfer dues nut depend un cell proliferation. High levels of gene transfer and IL-2 expression were also achieved in short-term cultures of primary human prostatic tumor cells established from tumor specimens obtained following radical prostatectomy of cancer patients. Depending on the type of liposome used, IL-2 levels secreted from the human prostatic tumor cells were comparable to or exceeded the levels of IL-2 secreted from retrovirally transduced MatLyLu cells, which induced antitumor immunity in the rat model. The ability to culture and expand ex vivo human prostatic tumor cells, and the use of a simple and highly efficient gene transfer method to generate genetically modified tumor vaccines, set the stage for clinical exploration of gene-based immunotherapy of prostate cancer.",
author = "J. Vieweg and D. Boczkowski and Roberson, {K. M.} and Edwards, {D. W.} and M. Philip and R. Philip and T. Rudoll and C. Smith and C. Robertson and Eli Gilboa",
year = "1995",
month = "1",
day = "1",
language = "English",
volume = "55",
pages = "2366--2372",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "11",

}

TY - JOUR

T1 - Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer

AU - Vieweg, J.

AU - Boczkowski, D.

AU - Roberson, K. M.

AU - Edwards, D. W.

AU - Philip, M.

AU - Philip, R.

AU - Rudoll, T.

AU - Smith, C.

AU - Robertson, C.

AU - Gilboa, Eli

PY - 1995/1/1

Y1 - 1995/1/1

N2 - We have shown previously that treatment of rats bearing the Dunning R3327 MatLyLu prostatic tumor with human interleukin 2 (IL-2) gene-modified tumor cell preparations induces potent antitumor immunity in the animal. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of prostate cancer, we have explored the use of a simplified gene delivery system based on liposomes to introduce and express the IL-2 gene in the Dunning rat R3327 MatLyLu prostatic tumor cell line (MatLyLu) and in short-term cultures of primary human prostatic tumor cells. Liposome-DNA complexes containing the adenoassociated virus inverted terminal repeats exhibited 3-10-fold higher levels of gene transfer and IL-2 expression than did liposome complexes with non-adeno-associated virus containing plasmids. Single transfections resulted in IL-2 expression for an extended period of time that exceeded severalfold the amount of IL-2 secreted from retrovirally transduced MatLyLu cells. X-irradiation of cells (4000 rads) prior to transfection did not affect cytokine secretion, indicating that liposome- mediated gene transfer dues nut depend un cell proliferation. High levels of gene transfer and IL-2 expression were also achieved in short-term cultures of primary human prostatic tumor cells established from tumor specimens obtained following radical prostatectomy of cancer patients. Depending on the type of liposome used, IL-2 levels secreted from the human prostatic tumor cells were comparable to or exceeded the levels of IL-2 secreted from retrovirally transduced MatLyLu cells, which induced antitumor immunity in the rat model. The ability to culture and expand ex vivo human prostatic tumor cells, and the use of a simple and highly efficient gene transfer method to generate genetically modified tumor vaccines, set the stage for clinical exploration of gene-based immunotherapy of prostate cancer.

AB - We have shown previously that treatment of rats bearing the Dunning R3327 MatLyLu prostatic tumor with human interleukin 2 (IL-2) gene-modified tumor cell preparations induces potent antitumor immunity in the animal. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of prostate cancer, we have explored the use of a simplified gene delivery system based on liposomes to introduce and express the IL-2 gene in the Dunning rat R3327 MatLyLu prostatic tumor cell line (MatLyLu) and in short-term cultures of primary human prostatic tumor cells. Liposome-DNA complexes containing the adenoassociated virus inverted terminal repeats exhibited 3-10-fold higher levels of gene transfer and IL-2 expression than did liposome complexes with non-adeno-associated virus containing plasmids. Single transfections resulted in IL-2 expression for an extended period of time that exceeded severalfold the amount of IL-2 secreted from retrovirally transduced MatLyLu cells. X-irradiation of cells (4000 rads) prior to transfection did not affect cytokine secretion, indicating that liposome- mediated gene transfer dues nut depend un cell proliferation. High levels of gene transfer and IL-2 expression were also achieved in short-term cultures of primary human prostatic tumor cells established from tumor specimens obtained following radical prostatectomy of cancer patients. Depending on the type of liposome used, IL-2 levels secreted from the human prostatic tumor cells were comparable to or exceeded the levels of IL-2 secreted from retrovirally transduced MatLyLu cells, which induced antitumor immunity in the rat model. The ability to culture and expand ex vivo human prostatic tumor cells, and the use of a simple and highly efficient gene transfer method to generate genetically modified tumor vaccines, set the stage for clinical exploration of gene-based immunotherapy of prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=0029057646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029057646&partnerID=8YFLogxK

M3 - Article

VL - 55

SP - 2366

EP - 2372

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 11

ER -