Combination therapy with AG-490 and interleukin 12 achieves greater antitumor effects than either agent alone.

Constitutive activation of Janus kinases (JAKs) and signal transducers and activators of transcription (STAT) occurs at very high frequency in various hematopoietic malignancies and solid tumors. It has been demonstrated that the tyrosine kinase inhibitor, AG-490, selectively blocks JAK activity and completely eliminates leukemia cells in a severe combined immunodeficient (SCID) mouse model. Because many cytokines, including interleukin (IL)-12, have been shown to signal through JAK/STAT pathways, AG-490 may inhibit cytokine-based cancer therapy.