Interleukin-12: A Cytokine at the Interface of Inflammation and Immunity

Prolonged and inducible transgene expression in the liver using gutless adenovirus: A potential therapy for liver cancer

“…IL-12 is a potent cytokine with robust antitumor effects. [27][28][29]32 The systemic administration of the recombinant protein to treat cancer has found the limitation of toxicity due to the ability of IL-12 to strongly induce interferon gamma production. 33,34 Adenovirus-mediated gene transfer of IL-12 to the tumor or peritumoral tissue causes a gradient of IL-12 concentration with higher values at the site of the neoplasm and lower systemic levels, resulting in increasing antitumor efficacy and wider therapeutic window.…”

“…Thus, to be effective, it would be necessary to infect peritumoral tissue with long-term expression vectors encoding cytokines endowed with potent immunostimulant and antiangiogenic properties such as IL-12. 31,32 However, these potent biological molecules are potentially toxic. 33,34 Hence, when using long-term expression vectors for transfer of antitumor cytokines, it would be essential to strictly control their expression to reach therapeutic levels while avoiding unwanted side effects.…”

Prevention of angiogenesis by naked DNA IL-12 gene transfer: angioprevention by immunogene therapy

“…27,28 Several studies have shown that IL-12 administration can induce tumor regression and rejection either alone or in combination with other immune stimuli or even antiangiogenic agents. While inhibition of angiogenesis has been observed, in most instances tumor rejection was associated with generation of a CD8 þ -mediated antitumor cell response.…”

Upregulation of natural killer cells functions underlies the efficacy of intratumorally injected dendritic cells engineered to produce interleukin-12

“…Interleukin-12 was identified as a factor that activates the function of natural killer (NK) cells [17,18]. NK cells express receptors for IL-12 and when stimulated with this cytokine potently upregulate their functions [19], as it has been also observed in vivo in human cancer patients treated systemically with this protein [20].…”

“…NK cells express receptors for IL-12 and when stimulated with this cytokine potently upregulate their functions [19], as it has been also observed in vivo in human cancer patients treated systemically with this protein [20]. It is possible that IL-12 acts not only by increasing the level of expression of effector molecules such as perforin and granzymes [17,18,21,22], Offprint requests to: Ignacio Melero, M.D., Ph.D., Facultad de Medicina, Universidad de Navarra, C/Irunlarrea 1, 31008 Pamplona, Spain but also by controlling the function or the expression of receptors triggering cytotoxicity [23]. Besides the elegant mechanisms that regulate whether or not engagement with a target cell causes its destruction in vitro [24][25][26], little is known about the real functions of NK cells in vivo.…”