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The aim of this study was to evaluate the inhibition of tumor growth induced by IL\u201013 delivered locally within or around transplanted tumor cells in mice. We observed that local administration of IL\u201013 at the site of transplanted tumor cells <jats:italic>in vivo<\/jats:italic> had potent inhibitory effects on growth of both immunogenic (P815 mastocytoma, H\u20102<jats:sup>d<\/jats:sup>) or nonimmunogenic (3LL lung carcinoma, H\u20102<jats:sup>b<\/jats:sup>) tumor cells. Mice injected with transfected P815 cells secreting large amounts of IL\u201013 rejected the P815 tumor and developed systemic specific anti\u2010tumor immunity leading to long\u2010lasting specific anti\u2010tumor protection. Less efficient anti\u2010tumoral effects were obtained with the nonimmunogenic 3LL tumor model when local administration of IL\u201013 was achieved by co\u2010inoculating xenogeneic chinese hamster ovary (CHO) IL\u201013 cells. Several local injections of CHO IL\u201013 cells were needed to obtain rejection of 3LL tumors and no induction of long\u2010lasting anti\u20103LL memory was obtained. Several studies were performed to elucidate the IL\u201013 anti\u2010tumoral effects. Experiments with nude mice indicated that IL\u201013 can also stimulate nonspecific anti\u2010tumor defenses. The histological examination of P815 IL\u201013 cells undergoing rejection showed monocytic cells and neutrophils infiltrating the tumor. Studies indicated that IL\u201013 administered <jats:italic>in vitro<\/jats:italic> did not directly stimulate the cytotoxicity of peritoneal macrophages and natural killer cells. However, experiments with Boyden chemotaxis chambers indicated that IL\u201013 was chemotactic for macrophages. Finally, preliminary experiments <jats:italic>in vitro<\/jats:italic> suggest that IL\u201013 improved antigenic presentation of P815 membranes. Thus, anti\u2010tumor effects of IL\u201013 <jats:italic>in vivo<\/jats:italic> most probably result from pleiotropic effects including recruitment of nonspecific cells and improved stimulation of immune\u2010specific anti\u2010tumor effectors.<\/jats:p>","DOI":"10.1002\/eji.1830250833","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T01:17:47Z","timestamp":1172798267000},"page":"2340-2348","source":"Crossref","is-referenced-by-count":35,"title":["Experimental gene therapy of cancer using tumor cells engineered to secrete interleukin\u201013"],"prefix":"10.1002","volume":"25","author":[{"given":"Sophie","family":"Lebel\u2010Binay","sequence":"first","affiliation":[]},{"given":"Brigitte","family":"Laguerre","sequence":"additional","affiliation":[]},{"given":"Fran\u00e7oise","family":"Quintin\u2010Colonna","sequence":"additional","affiliation":[]},{"given":"H\u00e9l\u00e8ne","family":"Conjeaud","sequence":"additional","affiliation":[]},{"given":"Marilyn","family":"Magazin","sequence":"additional","affiliation":[]},{"given":"Brigitte","family":"Miloux","sequence":"additional","affiliation":[]},{"given":"Florence","family":"Pecceu","sequence":"additional","affiliation":[]},{"given":"Daniel","family":"Caput","sequence":"additional","affiliation":[]},{"given":"Pascual","family":"Ferrara","sequence":"additional","affiliation":[]},{"given":"Didier","family":"Fradelizi","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,11,23]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-2478(88)90155-1"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.4.1217"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90591-2"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830210350"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/4.12.1429"},{"key":"e_1_2_1_7_2","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.4049\/jimmunol.149.11.3627","volume":"149","author":"Cavallo F.","year":"1992","journal-title":"J. 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