Intratumoral delivery of IL-18 naked DNA induces T-cell activation and Th1 response in a mouse hepatic cancer model

Abstract

Background: The novel cytokine, interleukin (IL)-18, is a strong interferon-γ inducer and costimulatory factor in Th1 cell activation. IL-18 triggers IFN-γ production and enhances cytolytic activity in both T and NK cells. However, the exact mechanism of antitumor action of IL-18 remains to be clarified. To determine the effects of IL-18 plasmid DNA on hepatic cancer in mice, CT26 murine colon adenocarcinoma cells were established in mouse liver.

Semliki Forest Virus Expressing Interleukin-12 Induces Antiviral and Antitumoral Responses in Woodchucks with Chronic Viral Hepatitis and Hepatocellular Carcinoma

“…Because long-term treatment with an adenoviral vector expressing IL-12 resulted in sustained antiviral effects in chronic WHV carrier woodchucks (13), repeated intratumoral administration of SFVenhIL-12 for the short-term expression of IL-12 in combination with peritumoral administration of the adenoviral vector for the long-term expression of IL-12 could be tested as a treatment strategy for HCC in woodchucks. The antitumoral efficacy of IL-15 and IL-18 has been demonstrated in several animal models of cancer (7,19,20,45,46,52), and a combination of SFV and adenoviral vectors expressing IL-12, IL-15, or IL-18 could be also tested in the woodchuck model for inducing sustained antitumoral effects.…”

Blocking NF-κB Is Essential for the Immunotherapeutic Effect of Recombinant IL18 in Pancreatic Cancer

“…IL18 can regulate both innate and adaptive immune responses through its effects on T cells (4,7,28), NK cells (29,30), macrophages (31), and DCs (32). Systemic administration of IL18 had little antitumor activity in several preclinical animal models (33).…”

“…IL18 is produced mainly by immune cells and effectively enhances innate and adaptive immune responses (4). IL18 stimulates T cells and enhances Th1 immune responses (5)(6)(7). It also has antitumor activity in preclinical models.…”

IL‐1, IL‐18, and IL‐33 families of cytokines

“…IL-18 induces Th1 responses and production of IFN-g, which play an important role in host defense. Intra-tumoral injection of IL-18 DNA enhanced IFN-g production and caused liver tumor regression (150). In addition, gene therapy with IL-18 can also serve as a powerful adjuvant when used in combination with a tumor antigen (151).…”