Prostate cancer gene therapy: Comparison of adenovirus-mediated expression of interleukin 12 with interleukin 12 plus B7-1 for in situ gene therapy and gene-modified, cell-based vaccines

G. W. Hull, M. A. McCurdy, Y. Nasu, C. H. Bangma, G. Yang, S. Shimura, H. M. Lee, J. Wang, J. Albani, S. Ebara, T. Sato, T. L. Timme, T. C. Thompson

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Abstract

We have documented previously that adenovirus-mediated interleukin 12 (IL-12) gene therapy is effective for orthotopic tumor control and suppression of pre-established metastases in a preclinical prostate cancer model (Y. Nasu et al., Gene Ther., 6: 338-349, 1999). In this report, we directly compare the effectiveness of an adenovirus that expresses both IL-12 and the costimulatory molecule B7-1 (AdmIL-12/B7) with one that expresses IL-12 alone (AdmIL-12) using the poorly immunogenic RM-9 orthotopic murine model of prostate cancer. We document AdmIL-12/B7-mediated secretion of IL-12 and increased surface expression of B7-1 in infected RM-9 tumor cells. A significant reduction in orthotopic tumor size and increased survival was demonstrated in mice treated with a single orthotopic injection of AdmIL-12/B7 compared with AdmIL-12 or controls. Six of 19 animals treated with AdmIL-12/B7 survived long term with apparent eradication of the primary tumor in contrast to one of 38 animals in the AdmIL-12-treated group. Orthotopic treatment of tumors with both vectors led to an infiltration of both CD4+ and CD8+ immunoreactive cells, with AdmIL-12/B7 treatment having a more prolonged infiltration of CD8+ cells. AdmIL-12/B7 was also more effective than AdmIL-12 or controls at suppression of pre-established metastases. We further developed a vaccine model based on s.c. injection of infected, irradiated RM-9 cells and found that both AdmIL-12 and AdmIL-12/B7 are effective at suppressing the development and growth of challenge orthotopic tumors using this protocol.

Original languageEnglish
Pages (from-to)4101-4109
Number of pages9
JournalClinical Cancer Research
Volume6
Issue number10
Publication statusPublished - Nov 13 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hull, G. W., McCurdy, M. A., Nasu, Y., Bangma, C. H., Yang, G., Shimura, S., Lee, H. M., Wang, J., Albani, J., Ebara, S., Sato, T., Timme, T. L., & Thompson, T. C. (2000). Prostate cancer gene therapy: Comparison of adenovirus-mediated expression of interleukin 12 with interleukin 12 plus B7-1 for in situ gene therapy and gene-modified, cell-based vaccines. Clinical Cancer Research, 6(10), 4101-4109.