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

Publication ,  Journal Article
Vieweg, J; Boczkowski, D; Roberson, KM; Edwards, DW; Philip, M; Philip, R; Rudoll, T; Smith, C; Robertson, C; Gilboa, E
Published in: Cancer Res
June 1, 1995

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 adeno-associated 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 does not depend on 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.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

June 1, 1995

Volume

55

Issue

11

Start / End Page

2366 / 2372

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Rats
  • Prostatic Neoplasms
  • Plasmids
  • Oncology & Carcinogenesis
  • Male
  • Liposomes
  • Interleukin-2
  • Humans
  • Genetic Therapy
 

Citation

APA
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ICMJE
MLA
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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 Res, 55(11), 2366–2372.
Vieweg, J., D. Boczkowski, K. M. Roberson, D. W. Edwards, M. Philip, R. Philip, T. Rudoll, C. Smith, C. Robertson, and E. Gilboa. “Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer.Cancer Res 55, no. 11 (June 1, 1995): 2366–72.
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 Res. 1995 Jun 1;55(11):2366–72.
Vieweg J, Boczkowski D, Roberson KM, Edwards DW, Philip M, Philip R, Rudoll T, Smith C, Robertson C, Gilboa E. Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer. Cancer Res. 1995 Jun 1;55(11):2366–2372.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

June 1, 1995

Volume

55

Issue

11

Start / End Page

2366 / 2372

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Rats
  • Prostatic Neoplasms
  • Plasmids
  • Oncology & Carcinogenesis
  • Male
  • Liposomes
  • Interleukin-2
  • Humans
  • Genetic Therapy