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

Clin Cancer Res. 2000 Oct;6(10):4101-9.


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 (AdmIL12/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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • B7-1 Antigen / genetics*
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cancer Vaccines*
  • Flow Cytometry
  • Genetic Therapy / methods*
  • Humans
  • Immunohistochemistry
  • Interleukin-12 / genetics*
  • Kinetics
  • Lung Neoplasms / therapy
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Prostatic Neoplasms / therapy*
  • Time Factors
  • Tumor Cells, Cultured


  • B7-1 Antigen
  • CD4 Antigens
  • CD8 Antigens
  • Cancer Vaccines
  • Interleukin-12