Antitumor Effects of IL-12 in Preclinical Studies

Abstract

The strong ability of IL-12 to stimulate many different mechanisms of innate and adaptive immunity (see previous chapter) corresponded to very potent antitumor effects of this cytokine observed in early studies in animal models of tumor therapy. This cytokine has been found effective in dozens of transplantable murine tumors, involving carcinomas, sarcomas, melanoma, and also hematologic malignancies, including poorly immunogenic tumors. Since IL-12 often exerted unacceptable toxic effects on normal tissues, at least when injected systemically, many attempts have been made to improve its therapeutic index by combination of this cytokine with various therapeutic agents and modalities: antibodies, tumor vaccines, other cytokines, antiangiogenic agents, chemotherapy, radiotherapy, and adoptive immunotherapy (Golab and Zagozdzon in Int J Mol Med 3: 537–544, 1999; Lasek et al. in Cancer Immunol Immunother 63: 419–435, 2014). To further attenuate IL-12-induced toxicities, in many recent preclinical treatment schemes, gene therapy approaches have been tested in which the IL-12 gene is introduced in various viral and non-viral vectors. Some of these approaches have been and are being applied in clinical trials. This chapter provides an overview of the most promising IL-12-based experimental strategies that have been recently tested in animal models of neoplasia.