| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory of Experimental Immunology, National Cancer Institute-Center for Cancer Research, Frederick, MD 21702; and Department of Microbiology, University of Nevada Medical School, Reno, NV 89557
In the present study, we have tested the ability of hydrodynamically delivered IL-2 cDNA to modulate the number and function of murine leukocyte subsets in different organs and in mice of different genetic backgrounds, and we have evaluated effects of this mode of gene delivery on established murine tumor metastases. Hydrodynamic administration of the IL-2 gene resulted in the rapid and transient production of up to 160 ng/ml IL-2 in the serum. The appearance of IL-2 was followed by transient production of IFN-
and a dramatic and sustained increase in NK cell numbers and NK-mediated cytolytic activity in liver and spleen leukocytes. In addition, significant increases in other lymphocyte subpopulations (e.g., NKT, T, and B cells) that are known to be responsive to IL-2 were observed following IL-2 cDNA plasmid delivery. Finally, hydrodynamic delivery of only 4 µg of the IL-2 plasmid to mice bearing established lung and liver metastases was as effective in inhibiting progression of metastases as was the administration of large amounts (100,000 IU/twice daily) of IL-2 protein. Studies performed in mice bearing metastatic renal cell tumors demonstrated that the IL-2 cDNA plasmid was an effective treatment against liver metastasis and moderately effective against lung metastasis. Collectively, these results demonstrate that hydrodynamic delivery of relatively small amounts of IL-2 cDNA provides a simple and inexpensive method to increase the numbers of NK and NKT cells, to induce the biological effects of IL-2 in vivo for use in combination with other biological agents, and for studies of its antitumor activity.
This article has been cited by other articles:
|
|
 |
|
  C. Bergamaschi, M. Rosati, R. Jalah, A. Valentin, V. Kulkarni, C. Alicea, G.-M. Zhang, V. Patel, B. K. Felber, and G. N. Pavlakis Intracellular Interaction of Interleukin-15 with Its Receptor {alpha} during Production Leads to Mutual Stabilization and Increased Bioactivity J. Biol. Chem., February 15, 2008; 283(7): 4189 - 4199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Subleski, V. L. Hall, T. C. Back, J. R. Ortaldo, and R. H. Wiltrout Enhanced Antitumor Response by Divergent Modulation of Natural Killer and Natural Killer T Cells in the Liver. Cancer Res., November 15, 2006; 66(22): 11005 - 11012. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Abdool, E. Cretney, A. D. Brooks, J. M. Kelly, J. Swann, A. Shanker, E. W. Bere Jr., W. M. Yokoyama, J. R. Ortaldo, M. J. Smyth, et al. NK Cells Use NKG2D to Recognize a Mouse Renal Cancer (Renca), yet Require Intercellular Adhesion Molecule-1 Expression on the Tumor Cells for Optimal Perforin-Dependent Effector Function J. Immunol., August 15, 2006; 177(4): 2575 - 2583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kamimura, Y. Sawa, M. Sato, E. Agung, T. Hirano, and M. Murakami IL-2 In Vivo Activities and Antitumor Efficacy Enhanced by an Anti-IL-2 mAb J. Immunol., July 1, 2006; 177(1): 306 - 314. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
