“…approaches can be divided into two types based on the proposed antitumor mechanism: (a) direct eradication of tumor cells after the introduction of genetic materials, e.g., a replacement or inactivation of defective genes such as p53 in tumor cells, leading to tumor cell apoptosis (11)(12)(13); or (b) indirect approaches mediated by immune cells, e.g., the introduction of immunostimulatory molecules or vectors encoding immunostimulatory transgenes to influence the immune milieu of the tumor, culminating in the introduction of antitumor immune responses. For this purpose, biological response modifiers such as Bacillus Calmette-Guérin were originally used intratumorally not only in animal models (14 -17) but also in clinical trials (18,19). Recently, particular cytokines [e.g., interleukin 2, tumor necrosis factor ␣, granulocyte macrophage colony-stimulating factor (GM-CSF), and interleukin 12] have been noted to elicit antitumor immunity effectively, and viral vectors (e.g., vaccinia virus and herpes simplex virus) encoding a cytokine have been injected intratumorally in animal models (4, 20 -26) and used in clinical trials (27,28).…”