Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production.

By J. Leonard, M. Sherman, G. Fisher, L. Buchanan, G. Larsen, M. Atkins, J. Sosman, J. Dutcher, N. Vogelzang, J. Ryan. 1997

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The Antibody-Based Delivery of Interleukin-12 to the Tumor Neovasculature Eradicates Murine Models of Cancer in Combination with Paclitaxel (2012, background): “ization of 12 of 17 patients and the death of 2 of them, with only one partial response (19).”
Type 1/Type 2 immunity in infectious diseases. (2001, background): “Early studies on the use of IL-2 and IL-12 in humans revealed their potential for severe systemic adverse effects [404, 405].”
Interleukin 12: still a promising candidate for tumor immunotherapy? (2014, background): “This initial priming dose of IL-12, given to determine the pharmacokinetic profile of the cytokine, was found critical for protection from the severe toxicity [119].”
Cytokines in clinical cancer immunotherapy (2018, background): “However, in clinical trials, the short half-life of the recombinant protein in serum meant that high and multiple doses were required, which resulted in dose-related toxicities, mainly caused by elevated levels of circulating IFN-γ.(80) To overcome the toxicities, different approaches have been prop”
Interluekin-12 enhances the function and anti-tumor activity in murine and human CD8+ T cells (2015, background): “The ex vivo dimension of these findings are especially cogent for IL-12 where significant in vivo clinical toxicity [44, 45] has limited the utilization of this promising cytokine and led investigators to look for non-systemic approaches.”