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+ T cells 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.