HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fernandez, N. C. Articles by Kourilsky, P. Search for Related Content PubMed PubMed Citation Articles by Fernandez, N. C. Articles by Kourilsky, P. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Genes and Gene Therapy

High Frequency of Specific CD8⁺ T Cells in the Tumor and Blood Is Associated with Efficient Local IL-12 Gene Therapy of Cancer¹

Nadine C. Fernandez^2,*, Jean-Pierre Levraud^2,, Hédi Haddada^*, Michel Perricaudet^* and Philippe Kourilsky^3,

^* Laboratoire de Vectorologie et Transfert de Gènes, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 1582, Institut Gustave Roussy, Villejuif, France; Unité de Biologie Moléculaire du Gène, Institut National de la Santé et de la Recherche Médicale Unité 277, Institut Pasteur, Paris, France

Cancer immunotherapy often aims at the reactivation and expansion of tumor-specific CTL. In an attempt to correlate in situ and/or systemic tumor-specific T cell expansion with tumor regression, we investigated the effects of adenovirus-mediated IL-12 or IFN- gene transfer into established P815 murine tumors. While IFN- was no more potent than the vector alone, IL-12 gene transfer promoted tumor eradication. Despite this antitumor effect, no significant cytolytic activity was detectable using classical cytotoxicity assays from in vitro restimulated splenocytes. Since intratumor gene delivery may induce a localized expansion of CTL, the presence of P815-specific CD8⁺ T cells in situ was assessed. Using the Immunoscope approach, we found a dramatic increase in clonotypic T cells at the tumor site following IL-12, but not IFN- gene delivery. Antitumor CD8⁺ T cell frequencies were then re-evaluated using this molecular detection technique, which revealed a comparable expansion of specific T cells in the peripheral organs, most strikingly in the blood. These data show that local IL-12 gene transfer, in contrast to IFN-, mediates a potent antitumor effect that correlates to clonal tumor-specific T cell expansions in situ and in the periphery.

This article has been cited by other articles:

				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]

				X.-c. Chen, R. Wang, X. Zhao, Y.-q. Wei, M. Hu, Y.-s. Wang, X.-w. Zhang, R. Zhang, L. Zhang, B. Yao, et al. Prophylaxis against carcinogenesis in three kinds of unestablished tumor models via IL12-gene-engineered MSCs Carcinogenesis, December 1, 2006; 27(12): 2434 - 2441. [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]

				F. Shi, A. L. Rakhmilevich, C. P. Heise, K. Oshikawa, P. M. Sondel, N.-S. Yang, and D. M. Mahvi Intratumoral Injection of Interleukin-12 Plasmid DNA, Either Naked or in Complex with Cationic Lipid, Results in Similar Tumor Regression in a Murine Model Mol. Cancer Ther., September 1, 2002; 1(11): 949 - 957. [Abstract] [Full Text] [PDF]

				Y. Wan, L. Lu, J. L. Bramson, S. Baral, Q. Zhu, A. Pilon, and K. Dayball Dendritic Cell-Derived IL-12 Is Not Required for the Generation of Cytotoxic, IFN-{gamma}-Secreting, CD8+ CTL In Vivo J. Immunol., November 1, 2001; 167(9): 5027 - 5033. [Abstract] [Full Text] [PDF]

				L. Peng, J. C. Krauss, G. E. Plautz, S. Mukai, S. Shu, and P. A. Cohen T Cell-Mediated Tumor Rejection Displays Diverse Dependence Upon Perforin and IFN-{gamma} Mechanisms That Cannot Be Predicted From In Vitro T Cell Characteristics J. Immunol., December 15, 2000; 165(12): 7116 - 7124. [Abstract] [Full Text] [PDF]

				P. Bousso, F. Lemaitre, J. Bilsborough, and P. Kourilsky Facing Two T Cell Epitopes: A Degree of Randomness in the Primary Response Is Lost Upon Secondary Immunization J. Immunol., July 15, 2000; 165(2): 760 - 767. [Abstract] [Full Text] [PDF]

				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]

				C. S. Schmidt and M. F. Mescher Adjuvant Effect of IL-12: Conversion of Peptide Antigen Administration from Tolerizing to Immunizing for CD8+ T Cells In Vivo J. Immunol., September 1, 1999; 163(5): 2561 - 2567. [Abstract] [Full Text] [PDF]