Preferences help
enabled [disable] Abstract
Number of results
2001 | 48 | 4 | 1077-1084
Article title

Combined delivery of an antiangiogenic protein (angiostatin) and an immunomodulatory gene (interleukin-12) in the treatment of murine cancer.

Title variants
Languages of publication
We investigated the feasibility of a novel therapeutic approach to treat neoplastic diseases in mice. This novel strategy consists in delivering a protein (angiostatin) with strong antiangiogenic properties, followed by administration of the interleukin 12 gene that is strongly immunomodulatory and has also some antiangiogenic effects. When angiostatin-mediated antiangiogenic therapy was used in combination with intratumor delivery of the IL-12 gene (a strategy much safer than IL-12 protein administration), this produced a synergistic therapeutic effect.
Physical description
  • Department of Molecular Biology, Center of Oncology-Maria Skłodowska-Curie Memorial Institute, Gliwice, Poland
  • Department of Molecular Biology, Center of Oncology-Maria Skłodowska-Curie Memorial Institute, Gliwice, Poland
  • Department of Molecular Biology, Center of Oncology-Maria Skłodowska-Curie Memorial Institute, Gliwice, Poland
  • Department of Molecular Biology, Center of Oncology-Maria Skłodowska-Curie Memorial Institute, Gliwice, Poland
  • 1. O'Reilly, M.S., Holmgren, L., Shing, Y., Chen, C., Rosenthal, R.A., Moses, M., Lane, W.S., Cao, Y., Sage, E.H. & Folkman, J. (1994) Angiostatin: A novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 79, 315-328.
  • 2. Ji, W.R., Castellino, F.J., Chang, Y., Deford, M.E., Gray, H., Villarreal, X., Kondri, M.E., Marti, D.N., Llinás, M., Schaller, J., Kramer, R.A. & Trail, P.A. (1998) Characterization of kringle domains of angiostatin as antagonists of endothelial cell migration, an important process in angiogenesis. FASEB J. 12, 1731-1738.
  • 3. Lucas, R., Holmgren, L., Garcia, I., Jimenez, B., Mandriota, S.J., Borlat, F., Sim, B.K.L., Wu, Z., Grau, G.E., Shing, Y., Soff, G.A., Bouck, N. & Pepper, M.S. (1998) Multiple forms of angiostatin induce apoptosis in endothelial cells. Blood 92, 4730-4741.
  • 4. Moser, T.L., Stack, M.S., Asplin, I., Enghild, J.J., Hojrup, P., Everitt, L., Hubchak, S., Schnaper, H.W. & Pizzo, S.V. (1999) Angiostatin binds ATP synthase on the surface of human endothelial cells. Proc. Natl. Acad. Sci. U.S.A. 96, 2811-2816.
  • 5. O'Reilly, M.S., Holmgren, L., Chen, C. & Folkman, J. (1996) Angiostatin induces and sustains dormancy of human primary tumors in mice. Nat. Med. 2, 689-692.
  • 6. Kirsch, M., Strasser, J., Allende, R., Bello, L., Zhang, J. & Black, P.ML. (1998) Angiostatin suppresses malignant glioma growth in vivo. Cancer Res. 58, 4654-4659.
  • 7. Sim, B.K.L., O'Reilly, M.S., Liang, H., Fortier, A.H., He, W., Madsen, J.W., Lapcevich, R. & Nacy, A. (1997) A recombinant human angiostatin protein inhibits experimental primary and metastaticcancer. Cancer Res. 57, 1329-1334.
  • 8. Mauceri, H.J., Hanna, N.N., Beckett, M.A., Gorski, D.H., Staba, M.-J., Stellato, K.A., Bigelow, K., Heimann, R., Gately, S., Dhanabal, M., Soff, G.A., Sukhatme, V.P., Kufe, D.W. & Weichselbaum, R.R. (1998) Combined effects of angiostatin and ionizing radiation in antitumour therapy. Nature 394, 287-291.
  • 9. Griscelli, F., Li, H., Cheong, C., Opolon, P., Bennaceur-Griscelli, A., Vassal, G., Soria, J., Soria, C., Lu, H., Perricaudet, M. & Yeh, P. (2000) Combined effects of radiotherapy and angiostatin gene therapy in glioma tumor model. Proc. Natl. Acad. Sci. U.S.A. 97, 6698-6703.
  • 10. Yokoyama, Y., Dhanabal, M., Griffioen, A.W., Sukhatme, V.P. & Ramakrishnan, S. (2000) Synergy between angiostatin and endostatin: Inhibition of ovarian cancer growth. Cancer Res. 60, 2190-2196.
  • 11. Feldman, A.L. & Libutti, S.K. (2000) Progress in antiangiogenic gene therapy of cancer. Cancer 89, 1181-1194.
  • 12. Tahara, H. & Lotze, M.T. (1995) Antitumor effects of interleukin-12 (IL-12): Applications for the immunotherapy and gene therapy of cancer. Gene Ther. 2, 96-106.
  • 13. Budryk, M., Wilczyńska, U., Szary, J. & Szala, S. (2000) Direct transfer of IL-12 gene into growing Renca tumors. Acta Biochim. Polon. 47, 385-391.
  • 14. Tan, J., Newton, C.A., Djeu, J.Y., Gutsch, D.E., Chang, A.E., Yang, N.S., Klein, T.W. & Hua, Y. (1996) Injection of complementary DNA encoding interleukin-12 inhibits tumor establishment at a distant site in a murine renal carcinoma model. Cancer Res. 56, 3399-3403.
  • 15. Obana, S., Miyazawa, H., Hara, E., Tamura, T., Nariuchi, H., Takata, M., Fujimoto, S. & Yamamoto, (1995) Induction of anti-tumor immunity by mouse tumor cells transfected with mouse interleukin-12gene. Jpn. J. Med. Sci. Biol. 48, 221-236.
  • 16. Gyorffy, S., Palmer, K., Podor, T.J., Hitt, M. & Gauldie, J. (2001) Combined treatment of a murine breast cancer model with type 5 adenovirus vectors expressing murine angiostatin and IL-12: A role for combined anti-angiogenesis and immunotherapy. J. Immunol. 166, 6212-6217.
Document Type
Publication order reference
YADDA identifier
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.