Interleukin (IL)-18 plays an important role in enhancing cellular immunity against
cancer and bacteria. We constructed retroviral and adenoviral vectors that show improved secretion of bioactive murine
IL-18 that could further enhance antitumor immunity in a murine model. Secretion of bioactive
IL-18 was facilitated by fusing the leader sequences of prepro-
parathyroid hormone (PTH) or
IL-1 receptor antagonist (IL-1ra) to the 5; end of the mature murine
IL-18 cDNA. Transfectants established by the retroviral vector carrying IL-1ra/IL-18 hybrid showed about 100-fold more
IL-18 production and
interferon (IFN)-gamma induction from splenocytes when compared with those carrying PTH/IL-18 hybrid. Repeated
intraperitoneal injection of an adenoviral vector with IL-1ra/IL-18 hybrid ligated to
IL-18 (Ad.IL-1ra.IL-18) successfully prevented establishment of human
colon cancer cells in the abdominal cavity of mice. Treatment with Ad.IL-1ra.IL-18 was associated with significantly elevated levels of serum
IL-18 and IFN- gamma.
IL-18 administration also enhanced the
cytostatic activity of peritoneal exudate cells against
cancer cells. These improved viral vectors, which efficiently produce bioactive
IL-18, could be used as a useful tool for cancer gene
therapy.