The Beneficial Effect of IL-12 and IL-18 Transduced Dendritic Cells Stimulated with Tumor Antigens on Generation of an Antitumor Response in a Mouse Colon Carcinoma Model

• Published in: Journal of Immunology Research Vol. 2022; pp. 7508928 - 24
• Main Authors: Mierzejewska, Jagoda, Węgierek-Ciura, Katarzyna, Rossowska, Joanna, Szczygieł, Agnieszka, Anger-Góra, Natalia, Szermer-Olearnik, Bożena, Geneja, Magdalena, Pajtasz-Piasecka, Elżbieta
• Format: Journal Article
• Language: English
• Published: Egypt Hindawi 25.03.2022; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Analysis; Animals; Antigen (tumor-associated); Antigens; Antigens, Neoplasm; Antitumor activity; B cells; Cancer; Carcinoma; CD4 antigen; CD8 antigen; Cell culture; Colon; Colon cancer; Colorectal cancer; Cytokines; Cytotoxicity; Dendritic Cells; Female; Gene therapy; Genetic engineering; Genetically modified organisms; Immunity; Immunology; Immunotherapy; Interleukin 1; Interleukin 12; Interleukin 18; Interleukin-12 - genetics; Interleukin-18 - genetics; Lymph nodes; Lymphatic system; Lymphocytes; Lymphocytes T; Medical equipment and supplies industry; Medical test kit industry; Mice; Mice, Inbred C57BL; Plasmids; T cells; Tumor antigens; Tumor Microenvironment; Tumors; Vaccines; Vectors (Biology); United States
• ISSN: 2314-8861; 2314-7156
• DOI: 10.1155/2022/7508928

The main purpose of our study was to determine the effect of dendritic cell (DC) transduction with lentiviral vectors carrying sequences of il18 and/or il12 genes on the level of antitumor activity in vitro and in vivo. We examined the ability of DCs to migrate to the tumor-draining lymph nodes and infiltrate tumor tissue and to activate the local and systemic antitumor response. On the 15th day, DCs genetically modified for production of IL-12 and/or IL-18 were administered peritumorally to C57BL/6 female mice with established MC38 tumors. Lymphoid organs and tumor tissue were collected from mice on the 3rd, 5th, and 7th days after a single administration of DCs for further analysis. Administration of DCs transduced for production of IL-12 alone and in combination with IL-18 increased the inflow and activity of CD4+ and CD8+ T lymphocytes in the tumor microenvironment and tumor-draining lymph nodes. We also found that even a single administration of such modified DCs could trigger a systemic antitumor response as well as inhibit tumor growth. Application of the developed DC-based vaccines may exert a favorable impact on stimulation of an antitumor immune response, especially if these DC vaccines are administered repeatedly.