Antitumor and Antimetastatic Activity of Interleukin-12

Interleukin-12 (IL-12) was identified independently by two groups. The first group, at Hoffmann-La Roche, was studying a cytokine, named cytotoxic lymphocyte maturation factor (CLMF), that activated cytolytic lymphocyte activities (Stern et al. 1990). The second group, at the Wistar Institute, was evaluating a cytokine, originally named natural killer (NK) cell stimulatory factor (NKSF), that could stimulate NK cell functions (Kobayashi et al. 1989). Once CLMF and NKSF were characterized and cloned, it became clear that this was in fact one molecule, which is now called IL-12. IL-12 has profound effects on both NK and T cells, including the ability to stimulate proliferation, cytolytic activity, and cytokine induction. Furthermore, it plays a major role in regulating the induction of T cell subsets and thus is an important component of the immune response to foreign antigens. Based on these properties, IL-12 was evaluated in animal models of malignancies and shown to have potent antitumor and antimetastatic activities. In this chapter, we will summarize some of the biological effects of IL-12 and show how these relate to the in vivo effects of this cytokine on malignancies. Additional information on IL-12 can be found in a number of review articles (Brunda 1994; Gately et al. 1994a; Brunda and Gately 1994; Trinchieri 1994; Gately and Brunda 1995; Brunda and Gately 1995; Hendrzak and Brunda 1995).