Antitumor effects of interleukin-12 in pre-clinical and early clinical studies (Review)

Interleukin-12 (IL-12) previously called cytotoxic lymphocyte maturation factor (CLMF) or NK cell stimulatory factor (NKSF) is a recently characterized heterodimeric cytokine composed of two subunits. Although identified no more than 19 years ago IL-12 has already proved efficacious in numerous pre-clinical tumor immunotherapy studies. Animal studies revealed that IL-12 has powerful antitumor, anti-metastatic and anti-angiogenic activities and seems to be less toxic than other immunotherapeutics such as interferons or IL-2. A number of pre-clinical studies with IL-12 prompted the evaluation of this cytokine in the treatment of human cancers. Results of phase I and early phase II clinical trials have already been reported and these are described here together with a brief discussion concerning IL-12-related toxicities and potential methods of their prevention.