| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Immunology, Vol 159, Issue 1 351-359, Copyright © 1997 by American Association of Immunologists
ARTICLES |
L Chen, D Chen, E Block, M O'Donnell, DW Kufe and SK Clinton
Dana-Farber Cancer Institute, Department of Urology, Harvard Medical School, Boston, MA 02115, USA.
IL-12 is a heterodimeric immunoregulatory cytokine composed of covalently linked p40 and p35 subunits and exhibits antitumor activity in a variety of laboratory models. The efficacy of systemically administered cytokines for cancer therapy is often limited by toxicity. The gene therapy approach provides a mechanism to achieve temporary and high local concentrations of cytokines within a tumor with less risk of systemic toxicity. We constructed replication-defective adenoviruses containing the murine IL-12 p40 subunit (Ad.mp40) or a bicistronic vector containing cDNAs for the p40 and p35 subunits (Ad.mIL-12). Murine MB49 bladder cancer cells infected with Ad.mIL-12 secrete high concentrations of biologically active IL-12, while those infected with Ad.mp40 produce the p40 homodimer. Tumors injected with Ad.mIL-12 show rapid increases in IL-12 and IFN-gamma expression over 2 to 5 days and a return to baseline by 7 to 14 days. Injection of tumors with Ad.mIL- 12 (1 x 10(9) plaque-forming units) results in a complete tumor regression in all mice, while those treated with control adenovirus succumb to their tumor. Efficacy is reduced when studies are performed in mice depleted of CD4+ and CD8+ cells or in nude mice. Mice cured of their tumor by Ad.mIL-12 demonstrate specific protective immunity upon rechallenge. Ad.mp40 does not exhibit antitumor activity and may antagonize the activity of rIL-12 or Ad.mIL-12. In summary, gene therapy strategies for cancer using adenoviral vectors containing IL-12 are highly effective with no significant toxicity in mice.
This article has been cited by other articles:
|
|
 |
|
  D.-J. Kim, J.-I. Youn, S.-H. Seo, H.-T. Jin, and Y.-C. Sung Differential Regulation of Antigen-Specific CD8+ T Cell Responses by IL-12p40 in a Dose-Dependent Manner J. Immunol., June 1, 2008; 180(11): 7167 - 7174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zhu, M. Waguespack, S. A. Barker, and S. Li Doxorubicin Directs the Accumulation of Interleukin-12 Induced IFN{gamma} into Tumors for Enhancing STAT1 Dependent Antitumor Effect Clin. Cancer Res., July 15, 2007; 13(14): 4252 - 4260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Meeran, S. Katiyar, C. A. Elmets, and S. K. Katiyar Interleukin-12 Deficiency Is Permissive for Angiogenesis in UV Radiation-Induced Skin Tumors Cancer Res., April 15, 2007; 67(8): 3785 - 3793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-S. Lee, J.-H. Kim, K.-J. Choi, I.-K. Choi, H. Kim, S. Cho, B. C. Cho, and C.-O. Yun Enhanced antitumor effect of oncolytic adenovirus expressing interleukin-12 and b7-1 in an immunocompetent murine model. Clin. Cancer Res., October 1, 2006; 12(19): 5859 - 5868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. Torrero, X. Xia, W. Henk, S. Yu, and S. Li Stat1 deficiency in the host enhances interleukin-12-mediated tumor regression. Cancer Res., April 15, 2006; 66(8): 4461 - 4467. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Meeran, S. K. Mantena, S. Meleth, C. A. Elmets, and S. K. Katiyar Interleukin-12-deficient mice are at greater risk of UV radiation-induced skin tumors and malignant transformation of papillomas to carcinomas. Mol. Cancer Ther., April 1, 2006; 5(4): 825 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zhou, E. A. Lafleur, N. V. Koshkina, L. L. Worth, M. S. Lester, and E. S. Kleinerman Interleukin-12 Up-Regulates Fas Expression in Human Osteosarcoma and Ewing's Sarcoma Cells by Enhancing Its Promoter Activity Mol. Cancer Res., December 1, 2005; 3(12): 685 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Harada, M. Shimada, S. Okano, T. Suehiro, Y. Soejima, Y. Tomita, and Y. Maehara IL-12 Gene Therapy Is an Effective Therapeutic Strategy for Hepatocellular Carcinoma in Immunosuppressed Mice J. Immunol., December 1, 2004; 173(11): 6635 - 6644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Russell, Q. Yan, G. Fan, A. P. Khalifah, D. K. Bishop, S. L. Brody, and M. J. Walter IL-12 p40 Homodimer-Dependent Macrophage Chemotaxis and Respiratory Viral Inflammation Are Mediated through IL-12 Receptor {beta}1 J. Immunol., December 15, 2003; 171(12): 6866 - 6874. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-F. Jia, L. L. Worth, C. L. Densmore, B. Xu, X. Duan, and E. S. Kleinerman Aerosol Gene Therapy with PEI: IL-12 Eradicates Osteosarcoma Lung Metastases Clin. Cancer Res., August 1, 2003; 9(9): 3462 - 3468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zhang and L. J. DeGroot Gene Therapy of a Rat Follicular Thyroid Carcinoma Model with Adenoviral Vectors Transducing Murine Interleukin-12 Endocrinology, April 1, 2003; 144(4): 1393 - 1398. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Fleet, L. Wang, O. Vitek, B. A. Craig, and H. J. Edenberg Gene expression profiling of Caco-2 BBe cells suggests a role for specific signaling pathways during intestinal differentiation Physiol Genomics, March 18, 2003; 13(1): 57 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. DeGroot and R. Zhang CLINICAL REVIEW 131: Gene Therapy for Thyroid Cancer: Where Do We Stand? J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 2923 - 2928. [Full Text] [PDF]
|
|
|
|
 |
|
 T. Maeyama, K. Kuwano, M. Kawasaki, R. Kunitake, N. Hagimoto, and N. Hara Attenuation of bleomycin-induced pneumopathy in mice by monoclonal antibody to interleukin-12 Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1128 - L1137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Kalinski, P. L. Vieira, J. H. N. Schuitemaker, E. C. de Jong, and M. L. Kapsenberg Prostaglandin E2 is a selective inducer of interleukin-12 p40 (IL-12p40) production and an inhibitor of bioactive IL-12p70 heterodimer Blood, June 1, 2001; 97(11): 3466 - 3469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Lafleur, S.-F. Jia, L. L. Worth, Z. Zhou, L. B. Owen-Schaub, and E. S. Kleinerman Interleukin (IL)-12 and IL-12 Gene Transfer Up-Regulate Fas Expression in Human Osteosarcoma and Breast Cancer Cells Cancer Res., May 1, 2001; 61(10): 4066 - 4071. [Abstract] [Full Text]
|
|
|
|
|
|
W. Li, L. Lu, Z. Wang, L. Wang, J. J. Fung, A. W. Thomson, and S. Qian IL-12 Antagonism Enhances Apoptotic Death of T Cells Within Hepatic Allografts from Flt3 Ligand-Treated Donors and Promotes Graft Acceptance J. Immunol., May 1, 2001; 166(9): 5619 - 5628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Walter, N. Kajiwara, P. Karanja, M. Castro, and M. J. Holtzman Interleukin 12 P40 Production by Barrier Epithelial Cells during Airway Inflammation J. Exp. Med., February 5, 2001; 193(3): 339 - 352. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Adris, E. Chuluyan, A. Bravo, M. Berenstein, S. Klein, M. Jasnis, C. Carbone, Y. Chernajovsky, and O. L. Podhajcer Mice Vaccination with Interleukin 12-transduced Colon Cancer Cells Potentiates Rejection of Syngeneic Non-Organ-related Tumor Cells Cancer Res., December 1, 2000; 60(23): 6696 - 6703. [Abstract] [Full Text]
|
|
|
|
|
|
K. J. Andrews, A. Ribas, L. H. Butterfield, C. M. Vollmer, F. C. Eilber, V. B. Dissette, S. D. Nelson, P. Shintaku, S. Mekhoubad, T. Nakayama, et al. Adenovirus-Interleukin-12-mediated Tumor Regression in a Murine Hepatocellular Carcinoma Model Is Not Dependent on CD1-restricted Natural Killer T Cells Cancer Res., November 1, 2000; 60(22): 6457 - 6464. [Abstract] [Full Text]
|
|
|
|
|
|
L. L. Worth, S.-F. Jia, Z. Zhou, L. Chen, and E. S. Kleinerman Intranasal Therapy with an Adenoviral Vector Containing the Murine Interleukin-12 Gene Eradicates Osteosarcoma Lung Metastases Clin. Cancer Res., September 1, 2000; 6(9): 3713 - 3718. [Abstract] [Full Text]
|
|
|
|
|
|
R. Mortarini, A. Borri, G. Tragni, I. Bersani, C. Vegetti, E. Bajetta, S. Pilotti, V. Cerundolo, and A. Anichini Peripheral Burst of Tumor-specific Cytotoxic T Lymphocytes and Infiltration of Metastatic Lesions by Memory CD8+ T Cells in Melanoma Patients Receiving Interleukin 12 Cancer Res., July 1, 2000; 60(13): 3559 - 3568. [Abstract] [Full Text]
|
|
|
|
|
|
K. Dunussi-Joannopoulos, K. Runyon, J. Erickson, R. G. Schaub, R. G. Hawley, and J. P. Leonard Vaccines With Interleukin-12-Transduced Acute Myeloid Leukemia Cells Elicit Very Potent Therapeutic and Long-Lasting Protective Immunity Blood, December 15, 1999; 94(12): 4263 - 4273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Watanabe, R. G. Fenton, J. M. Wigginton, K. L. McCormick, K. M. Volker, W. E. Fogler, P. G. Roessler, and R. H. Wiltrout Intradermal Delivery of IL-12 Naked DNA Induces Systemic NK Cell Activation and Th1 Response In Vivo That Is Independent of Endogenous IL-12 Production J. Immunol., August 15, 1999; 163(4): 1943 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Jiang, D. M. Magee, and R. A. Cox Construction of a Single-Chain Interleukin-12-Expressing Retroviral Vector and Its Application in Cytokine Gene Therapy against Experimental Coccidioidomycosis Infect. Immun., June 1, 1999; 67(6): 2996 - 3001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Hirschowitz and R. G. Crystal Adenovirus-Mediated Expression of Interleukin-12 Induces Natural Killer Cell Activity and Complements Adenovirus-Directed gp75 Treatment of Melanoma Lung Metastases Am. J. Respir. Cell Mol. Biol., May 1, 1999; 20(5): 935 - 941. [Abstract] [Full Text]
|
|
|
|
|
|
F. Huaux, C. Lardot, M. Arras, M. Delos, M.-C. Many, J.-P. Coutelier, J.-P. Buchet, J.-C. Renauld, and D. Lison Lung Fibrosis Induced by Silica Particles in NMRI Mice Is Associated with an Upregulation of the p40 Subunit of Interleukin-12 and Th-2 Manifestations Am. J. Respir. Cell Mol. Biol., April 1, 1999; 20(4): 561 - 572. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. D. Car, V. M. Eng, J. M. Lipman, and T. D. Anderson The Toxicology of Interleukin-12: A Review Toxicol Pathol, January 1, 1999; 27(1): 58 - 63. [Abstract] [PDF]
|
|
|
|
|
|
N. C. Fernandez, J.-P. Levraud, H. Haddada, M. Perricaudet, and P. Kourilsky High Frequency of Specific CD8+ T Cells in the Tumor and Blood Is Associated with Efficient Local IL-12 Gene Therapy of Cancer J. Immunol., January 1, 1999; 162(1): 609 - 617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Siders, P. W. Wright, J. A. Hixon, W. G. Alvord, T. C. Back, R. H. Wiltrout, and R. G. Fenton T Cell- and NK Cell-Independent Inhibition of Hepatic Metastases by Systemic Administration of an IL-12-Expressing Recombinant Adenovirus J. Immunol., June 1, 1998; 160(11): 5465 - 5474. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gong, D. Chen, M. Kashiwaba, Y. Li, L. Chen, H. Takeuchi, H. Qu, G. J. Rowse, S. J. Gendler, and D. Kufe Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells PNAS, May 26, 1998; 95(11): 6279 - 6283. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
