Generation of antitumor response by IL-2-transduced JAWS II dendritic cells

• Published in: Immunobiology (1979) Vol. 216; no. 10; pp. 1074 - 1084
• Main Authors: Rossowska, Joanna, Pajtasz-Piasecka, Elżbieta, Ryśnik, Oliwia, Wojas, Justyna, Krawczenko, Agnieszka, Szyda, Anna, Duś, Danuta
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier GmbH 01.10.2011
• Subjects: Advanced Basic Science; Allergy and Immunology; Animals; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Antitumor immunotherapy; Cancer Vaccines - immunology; Cell Movement - immunology; Cell vaccination; Colonic Neoplasms - immunology; Colonic Neoplasms - pathology; Colonic Neoplasms - therapy; Dendritic Cells - immunology; Disease Models, Animal; Experimental MC38 colon carcinoma; Female; IL-2-Transduced dendritic cells; Immunity, Cellular; Immunophenotyping; Immunotherapy, Adoptive; Interleukin-2 - biosynthesis; Interleukin-2 - genetics; Kaplan-Meier Estimate; Lymph Nodes - immunology; Mice; Mice, Inbred C57BL; Neoplasms, Experimental - immunology; Neoplasms, Experimental - therapy; Phenotype; Th1 Cells - immunology; Transduction, Genetic; tumor antigen; Antitumor immunotherapy; dendritic cells; Cell vaccination; DCs; TAg; Experimental MC38 colon carcinoma; MC38; murine colon carcinoma; IL-2-Transduced dendritic cells
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2011.05.006

Abstract Antigen-loaded dendritic cells (DCs) are a promising tool for inducing a tumor-specific immune response. It seems probable that co-administration of those cells together with cytokine-transduced DCs can further increase effectiveness of the antitumor vaccine. The local production of IL-2 by genetically modified DCs may result in alteration of the unfavorable tumor environment causing immune response dysfunction. In the presented study murine DCs of an established JAWS II cell line were transduced with a retroviral vector carrying murine IL-2 gene (JAWS II/IL-2). JAWS II/IL-2 cells demonstrated slightly decreased tumor antigen (TAg) uptake capacities. However, this modification resulted in enhanced ability of the cells to migrate in vivo . The multiple injection of vaccines containing JAWS II/IL-2 cells caused MC38 tumor growth delay and prolonged mice survival. The immunological response was manifested as cytotoxic natural killer (NK) and T cell activation and tumor tissue infiltration by CD8+ and CD4+ cells, accompanied by increased IFN-γ production by spleen cells. These observations suggest that repeated peritumoral administration of IL-2-producing dendritic cells can inhibit tumor growth by intensification of CD8+ and CD4+ cells’ influx into tumor tissue and further activation of the systemic antitumor response. It can be concluded that IL-2 transduced dendritic cells may be used as a potent adjuvant in antitumor immunotherapy.