| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada
In this study, we used intratumor delivery of adenoviral vectors to induce a selective anti-tumor response by combining the potent angiogenesis inhibitor murine angiostatin (adenovirus (Ad)-angiostatin) with the powerful immune simulator and angiostatic cytokine murine IL-12 (Ad-IL-12). In a murine model of breast carcinoma, intratumor injection of Ad-angiostatin delayed mean tumor growth, as compared with control virus with an initial regression of tumor growth, in 65% of treated animals. However, all treated animals eventually succumbed to the tumors. Mice injected with Ad-IL-12 alone responded with an initial regression in 20% of treated animals, with only 13% developing a total regression. Coinjection of the vectors resulted in 96% of the treated animals developing an initial regression, with 54% undergoing a total regression of the tumor. These mice were resistant to tumor rechallenge and developed a strong CTL response. Frozen tumor sections were stained for microvessel density using an Ab against murine CD31, an endothelial cell marker. Automated image analysis revealed the mean microvessel density following the administration of Ad-angiostatin and Ad-IL-12 alone or in combination was significantly reduced compared with the control-treated tumor. In summary, we have shown that a short-term course of antiangiogenic therapy combined with immunotherapy can effectively shrink a solid tumor and vaccinate the animal against rechallenge. The rationale for this therapy is to limit the tumor size by attacking the vasculature with angiostatin, thereby allowing IL-12 to mount a T cell-specific response against the tumor Ag.
This article has been cited by other articles:
|
|
 |
|
  M. M. Seavey, P. C. Maciag, N. Al-Rawi, D. Sewell, and Y. Paterson An Anti-Vascular Endothelial Growth Factor Receptor 2/Fetal Liver Kinase-1 Listeria monocytogenes Anti-Angiogenesis Cancer Vaccine for the Treatment of Primary and Metastatic Her-2/neu+ Breast Tumors in a Mouse Model J. Immunol., May 1, 2009; 182(9): 5537 - 5546. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Morioka, L. Weissbach, T. Vogel, G. P. Nielsen, G. T. Faircloth, L. Shao, and F. J. Hornicek Antiangiogenesis Treatment Combined with Chemotherapy Produces Chondrosarcoma Necrosis Clin. Cancer Res., March 1, 2003; 9(3): 1211 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Scappaticci Mechanisms and Future Directions for Angiogenesis-Based Cancer Therapies J. Clin. Oncol., September 15, 2002; 20(18): 3906 - 3927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Dabrosin, S. Gyorffy, P. Margetts, C. Ross, and J. Gauldie Therapeutic Effect of Angiostatin Gene Transfer in a Murine Model of Endometriosis Am. J. Pathol., September 1, 2002; 161(3): 909 - 918. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Margetts, S. Gyorffy, M. Kolb, L. Yu, C. M. Hoff, C. J. Holmes, and J. Gauldie Antiangiogenic and Antifibrotic Gene Therapy in a Chronic Infusion Model of Peritoneal Dialysis in Rats J. Am. Soc. Nephrol., March 1, 2002; 13(3): 721 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-I Ma, P. Guo, J. Li, S.-Z. Lin, Y.-H. Chiang, X. Xiao, and S.-Y. Cheng Suppression of Intracranial Human Glioma Growth after Intramuscular Administration of an Adeno-associated Viral Vector Expressing Angiostatin Cancer Res., February 1, 2002; 62(3): 756 - 763. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
