Suppression of the tumorigenic growth of Burkitt's lymphoma cells in immunodeficient mice by cytokine gene transfer using EBV‐derived episomal expression vectors

• Published in: International journal of cancer Vol. 86; no. 3; pp. 301 - 306
• Main Authors: Mücke, Susanne, Draube, Andreas, Polack, Axel, Pawlita, Michael, Massoudi, Nadia, Staratschek‐Jox, Andrea, Bohlen, Heribert, Bornkamm, Georg, Diehl, Volker, Wolf, Jürgen
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.05.2000; Wiley-Liss
• Subjects: Animals; Biological and medical sciences; Burkitt Lymphoma - genetics; Burkitt Lymphoma - immunology; Burkitt Lymphoma - prevention & control; Cell Division - genetics; Cytokines - genetics; Gene Expression Regulation, Neoplastic; Gene Transfer Techniques; Genes, Viral; Genetic Therapy; Genetic Vectors; Hematologic and hematopoietic diseases; Herpesvirus 4, Human; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Mice; Mice, Nude; Neoplasm Transplantation; Other treatments; Plasmids; Treatment. General aspects; Tumors; Epstein Barr virus; Interleukin 4; Lymphoproliferative syndrome; Gammaherpesvirinae; Immune response; Herpesviridae; Treatment efficiency; Rodentia; Cytokine; Burkitt lymphoma; Malignant hemopathy; Non Hodgkin lymphoma; Experimental study; Genetic transfer; Infection; Virus; Vertebrata; Immunosuppression; Mammalia; Mouse; Viral disease; Animal; Interleukin 10; Gene therapy; Comparative study
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(20000501)86:3<301::AID-IJC1>3.0.CO;2-2

Epstein‐Barr virus (EBV)‐based expression vectors were tested for cytokine gene transfer‐mediated induction of an immune response against human lymphoma cells. These vectors express the EBV latent gene EBNA 1 and carry the EBV latent origin of replication (ori P) for episomal replication in transfected cells. In addition, 3 human immunoglobulin light chain enhancer elements augment expression in B‐cells. The suitability of these vectors for expression of cytokine genes in human lymphoma cells in vitro has been demonstrated. In order to extend these experiments in vivo, highly tumorigenic Burkitt's lymphoma (BL) cells were transfected with different cytokine genes of human and murine origin cloned into the EBNA 1/ori P vectors. Tumorigenicity of the transfectants was measured after inoculation into nude mice. No effect on tumorigenicity was observed after hIL 6 transfection and an inconsistent effect after hTNFα transfection. In contrast, complete suppression of tumor outgrowth occurred in hIL 10 transfectants. This tumor suppressive effect, however, was restricted to the IL 10 transfectants themselves and not directed against non‐transfected cells. By comparison, mIL 4 transfected BL cells also were non‐tumorigenic. However, co‐inoculation of mIL 4 transfected and non transfected cells resulted in suppression of the tumorigenicity of the non‐transfected cells. Thus, highly tumorigenic BL cells in nude mice are sensitive to immune effector mechanisms triggered by cytokine expression. In this experimental model, EBNA 1/ori P expression vectors are a suitable tool for cytokine gene transfer mediated induction of an anti‐lymphoma immune response of the host. Int. J. Cancer 86:301–306, 2000. © 2000 Wiley‐Liss, Inc.