Genetically engineered recombinant adenovirus expressing interleukin‑2 for hepatocellular carcinoma therapy.

Abstract

Regulatory and effector T cells possess immunological cytotoxicity for tumor cells in the tumor microenvironment during tumor progression and are the primary suppressors inhuman cancer therapy. Interleukin‑2 (IL‑2) is an anticancer cytokine, which triggers human innate and adaptive immunity by stimulating T cell propagation and lymphocyte infiltration into tumor sites. IL‑2 has been used successfully for cancer therapy. Recombinant adenovirus expressing IL‑2 (rAd‑IL‑2) injection is a gene therapy agent that may improve prognosis of hepatocellular carcinoma (HCC) patients. In the present study, the ability of IL‑2 to stimulate an immune response and the ability of recombinant adenovirus to inhibit tumor cell growth in HCC was investigated in a HCC tumor model. It was demonstrated that the regulatory and effector cell‑mediated tumor suppression by antitumor cluster of differentiation (CD)4+ and CD8+ Tcells stimulated by rAd‑IL‑2 is tumor‑specific. Furthermore, rAd‑IL‑2 significantly stimulated tumor‑specific cytotoxic T lymphocyte responses, increased interferon‑γ release and enhanced antitumor immunity by inducing CD4+ and CD8+ T cell recruitment into the tumor, and additionally induced memory to protect tumor‑bearing mice against tumor challenge. Treatment with rAd‑IL‑2 led to tumor regression and long‑term survival of mice in the 120‑day treatment period. Tumor challenge experiments demonstrated that rAd‑IL‑2 induced memory, protecting against reinfection. In conclusion, rAd‑IL‑2 may promote tumor‑associated effector and regulatory T cell expansion and may be a potential therapeutic agent for clinical immunotherapy application in the treatment of cancer.