title: Enhanced eradication of local and distant tumors by genetically produced interleukin-12 and radiation.
abstract: Ionizing radiation (IR) is frequently unsuccessful in the treatment of cancer because of local failure or distant metastases. The efficacy of systemically administered cytokines for cancer therapy is often limited by toxicity. We report that intratumoral injection of an adenoviral vector with interleukin-12 (IL-12) enhances local anti-tumor effects of irradiation (IR). We demonstrate that microscopic tumor growth at a distant site is suppressed following treatment of the primary tumor with adeno-murine IL-12 (Adm.IL-12). The results support a model in which the anti-angiogenic effects of IL-12 contribute to the local anti-tumor effects of radiation, while IL-12 induced immunity suppresses growth of microscopic tumors distant from the primary irradiated site. These data suggest that combining radiotherapy with IL-12 improves both local and distant tumor control compared to either treatment alone. Immunoradiotherapy may be employed in addition to or in place of current conventional therapies to increase local control and decrease distant tumor growth.
authors.affiliation: Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: S
authors.initials: S
authors.lastname: Seetharam
authors.forename: M J
authors.initials: MJ
authors.lastname: Staba
authors.forename: L P
authors.initials: LP
authors.lastname: Schumm
authors.forename: K
authors.initials: K
authors.lastname: Schreiber
authors.forename: H
authors.initials: H
authors.lastname: Schreiber
authors.forename: D W
authors.initials: DW
authors.lastname: Kufe
authors.forename: R R
authors.initials: RR
authors.lastname: Weichselbaum
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005354:Fibrosarcoma / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism / Q000532:radiotherapy*; D005822:Genetic Vectors; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000276:immunology* / Q000378:metabolism / Q000532:radiotherapy*; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000532:radiotherapy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D016499:Radioimmunotherapy; D012044:Regression Analysis; D012074:Remission Induction; D014407:Tumor Cells, Cultured
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018664:Interleukin-12