This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, R. Articles by DeGroot, L. J. Search for Related Content PubMed PubMed Citation Articles by Zhang, R. Articles by DeGroot, L. J. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Genes and Gene Therapy Thyroid Cancer

Effective Genetic Therapy of Established Medullary Thyroid Carcinomas with Murine Interleukin-2: Dissemination and Cytotoxicity Studies in a Rat Tumor Model¹

Thyroid Study Unit/MC 3090 (R.Z., L.J.D.), Department of Medicine, Department of Pathology (F.H.S.), The University of Chicago, Chicago, Illinois 60637

Address all correspondence and requests for reprints to: Leslie J. DeGroot, M.D., Thyroid Study Unit, Mail Code 3090, The University of Chicago, 5841 South Maryland Avenue, Chicago, Illinois 60637.

Replication-defective adenovirus (AdCMVmIL2) expressing murine interleukin-2 was directly injected into rat medullary thyroid carcinomas to examine antitumor activity. AdCMVmIL2 cured 42.9% of all treated tumor bearing animals. Most cured rats were protected against tumor growth after subsequent rechallenge with wild-type tumor cells, reflecting the immunity obtained from the original treatment. Studies of viral dissemination showed that the intratumoral inoculated viruses can enter the circulation, infect peripheral tissues, and express genes driven by the CMV promoter. Liver is the main target organ. In a toxicity study, AdCMVmIL2 was administered iv at a dose five times higher than that given directly into tumor. No detectable side effect was found. Histological studies showed variable degrees of lymphocyte infiltration in the livers of studied animals, and no functional change indicated by the normal serum level of glutamic oxalacetic transaminase and glutamic pyruvic transaminase was found in all animals studied. These data demonstrate that AdCMVmIL2 is an effective antitumor agent in this animal model, and that virus treatment can be given without significant toxicity to other organs.

This article has been cited by other articles:

				W. Walther, F. Arlt, I. Fichtner, J. Aumann, U. Stein, and P. M. Schlag Heat-inducible in vivo gene therapy of colon carcinoma by human mdr1 promoter-regulated tumor necrosis factor-{alpha} expression Mol. Cancer Ther., January 1, 2007; 6(1): 236 - 243. [Abstract] [Full Text] [PDF]

				F. Siddiqui, C.-Y. Li, S. M. LaRue, J. M. Poulson, P. R. Avery, A. F. Pruitt, X. Zhang, R. L. Ullrich, D. E. Thrall, M. W. Dewhirst, et al. A phase I trial of hyperthermia-induced interleukin-12 gene therapy in spontaneously arising feline soft tissue sarcomas Mol. Cancer Ther., January 1, 2007; 6(1): 380 - 389. [Abstract] [Full Text] [PDF]

				Y. Wang, H. Wang, C.-Y. Li, and F. Yuan Effects of rate, volume, and dose of intratumoral infusion on virus dissemination in local gene delivery. Mol. Cancer Ther., February 1, 2006; 5(2): 362 - 366. [Abstract] [Full Text] [PDF]

				Y. Wang, S. Liu, C.-Y. Li, and F. Yuan A Novel Method for Viral Gene Delivery in Solid Tumors Cancer Res., September 1, 2005; 65(17): 7541 - 7545. [Abstract] [Full Text] [PDF]

				N. Cengic, C. H. Baker, M. Schutz, B. Goke, J. C. Morris, and C. Spitzweg A Novel Therapeutic Strategy for Medullary Thyroid Cancer Based on Radioiodine Therapy following Tissue-Specific Sodium Iodide Symporter Gene Expression J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4457 - 4464. [Abstract] [Full Text] [PDF]

				Y. Wang, J. K. Hu, A. Krol, Y.-P. Li, C.-Y. Li, and F. Yuan Systemic dissemination of viral vectors during intratumoral injection Mol. Cancer Ther., November 1, 2003; 2(11): 1233 - 1242. [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]

				M. Messina, D. M. T. Yu, G. W. Both, P. L. Molloy, and B. G. Robinson Calcitonin-Specific Transcription and Splicing Targets Gene-Directed Enzyme Prodrug Therapy to Medullary Thyroid Carcinoma Cells J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1310 - 1318. [Abstract] [Full Text] [PDF]

				R. Zhang, F. H. Straus, and L. J. DeGroot Cell-Specific Viral Gene Therapy of a Hurthle Cell Tumor J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1407 - 1414. [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]

				F. Lohr, D. Y. Lo, D. A. Zaharoff, K. Hu, X. Zhang, Y. Li, Y. Zhao, M. W. Dewhirst, F. Yuan, and C.-Y. Li Effective Tumor Therapy with Plasmid-encoded Cytokines Combined with in Vivo Electroporation Cancer Res., April 1, 2001; 61(8): 3281 - 3284. [Abstract] [Full Text]

				K. Haupt, F. Siegel, M. Lu, D. Yang, G. Hilken, K. Mann, M. Roggendorf, and B. Saller Induction of a Cellular and Humoral Immune Response against Preprocalcitonin by Genetic Immunization: A Potential New Treatment for Medullary Thyroid Carcinoma Endocrinology, March 1, 2001; 142(3): 1017 - 1023. [Abstract] [Full Text] [PDF]

				Q. Huang, J. K. Hu, F. Lohr, L. Zhang, R. Braun, J. Lanzen, J. B. Little, M. W. Dewhirst, and C.-Y. Li Heat-induced Gene Expression as a Novel Targeted Cancer Gene Therapy Strategy Cancer Res., July 1, 2000; 60(13): 3435 - 3439. [Abstract] [Full Text]

				A. Boland, M. Ricard, P. Opolon, J.-M. Bidart, P. Yeh, S. Filetti, M. Schlumberger, and M. Perricaudet Adenovirus-mediated Transfer of the Thyroid Sodium/Iodide Symporter Gene into Tumors for a Targeted Radiotherapy Cancer Res., July 1, 2000; 60(13): 3484 - 3492. [Abstract] [Full Text]