Study of cancer gene therapy using IL-12-secreting endothelial progenitor cells in a rat solid tumor model.

Mariko Muta, Gaku Matsumoto, Kiyoshi Hiruma, Emi Nakashima, Masakazu Toi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

To test the hypothesis that genetically modified bone marrow-derived endothelial progenitor cells (EPCs) can be effective carriers of therapeutic agents to tumor sites, we utilized our conditionally immortalized endothelial progenitor cell line, TR-BME-2. In the syngenic rat, systemically injected TR-BME-2 cells were immediately distributed to the organs (lung, bone marrow, peripheral blood, liver, spleen). Trapped cells were cleared within 4 days, but selective accumulation in the Walker256 tumor was maintained for over 4 days. The tumor growth was enhanced by administration of TR-BME-2 cells. It is suggested that accumulated TR-BME-2 differentiated to tumor vasculature, increased the tumor blood supply, and thereby increased the tumor volume. We conducted IL-12 gene transfection of TR-BME-2 cells with a virus vector in vitro, and used the resultant IL-12-secreting TR-BME-2 to deliver IL-12, which strongly activates cytotoxic lymphocytes and natural killer cells, to the tumor site in vivo. However, the tumor-progressive character of TR-BME-2 offset the anti-tumor effect of IL-12. Nevertheless, our results suggest that gene-transfected EPCs could be useful as a tumor-specific drug delivery system, especially if the tumor vasculature-promoting effect of EPCs can be blocked.

Original languageEnglish
Pages (from-to)1765-1769
Number of pages5
JournalOncology Reports
Volume10
Issue number6
Publication statusPublished - 2003 Nov
Externally publishedYes

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Neoplasm Genes
Interleukin-12
Genetic Therapy
Neoplasms
Bone Marrow
Endothelial Progenitor Cells
Drug Delivery Systems
TR-2 mycotoxin
Tumor Burden
Natural Killer Cells
Genes
Transfection
Spleen
Lymphocytes
Viruses
Cell Line
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Muta, M., Matsumoto, G., Hiruma, K., Nakashima, E., & Toi, M. (2003). Study of cancer gene therapy using IL-12-secreting endothelial progenitor cells in a rat solid tumor model. Oncology Reports, 10(6), 1765-1769.

Study of cancer gene therapy using IL-12-secreting endothelial progenitor cells in a rat solid tumor model. / Muta, Mariko; Matsumoto, Gaku; Hiruma, Kiyoshi; Nakashima, Emi; Toi, Masakazu.

In: Oncology Reports, Vol. 10, No. 6, 11.2003, p. 1765-1769.

Research output: Contribution to journalArticle

Muta, M, Matsumoto, G, Hiruma, K, Nakashima, E & Toi, M 2003, 'Study of cancer gene therapy using IL-12-secreting endothelial progenitor cells in a rat solid tumor model.', Oncology Reports, vol. 10, no. 6, pp. 1765-1769.
Muta, Mariko ; Matsumoto, Gaku ; Hiruma, Kiyoshi ; Nakashima, Emi ; Toi, Masakazu. / Study of cancer gene therapy using IL-12-secreting endothelial progenitor cells in a rat solid tumor model. In: Oncology Reports. 2003 ; Vol. 10, No. 6. pp. 1765-1769.
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