Interleukin 12: still a promising candidate for tumor immunotherapy?

Abstract

Interleukin 12 (IL-12) seemed to represent the ideal candidate for tumor immunotherapy, due to its ability to activate both innate (NK cells) and adaptive (cytotoxic T lymphocytes) immunities. However, despite encouraging results in animal models, very modest antitumor effects of IL-12 in early clinical trials, often accompanied by unacceptable levels of adverse events, markedly dampened hopes of the successful use of this cytokine in cancer patients. Recently, several clinical studies have been initiated in which IL-12 is applied as an adjuvant in cancer vaccines, in gene therapy including locoregional injections of IL-12 plasmid and in the form of tumor-targeting immunocytokines (IL-12 fused to monoclonal antibodies). The near future will show whether this renewed interest in the use of IL-12 in oncology will result in meaningful therapeutic effects in a select group of cancer patients.

CD1b-autoreactive T cells recognize phospholipid antigens and contribute to antitumor immunity against a CD1b+T cell lymphoma

“…However, clinical trials have yielded mixed results, mostly due to over stimulation of the immune system and related adverse side effects or the lack of apparent benefits over existing treatment options. 38,46 Nevertheless, recent efforts have been directed toward delivering these agents to the local tumor microenvironment and in conjunction with other immunotherapies like T cell adoptive transfer.…”

“…Interestingly, both CpG and IL-12 have been used in pre-clinical studies as anticancer therapy. 38,46 Both these immunostimulatory agents work to increase the production of IFNg by innate and adaptive immune cells. However, clinical trials have yielded mixed results, mostly due to over stimulation of the immune system and related adverse side effects or the lack of apparent benefits over existing treatment options.…”

Melanoma Treatment with Intratumoral Electroporation of Tavokinogene Telseplasmid (pIL-12, Tavokinogene Telseplasmid)

“…IL-12 is a key Th1-polarizing cytokine along with IFN-γ [20]. In addition to priming and maintaining T helper and cytotoxic cell responses to specific antigens and the subsequent production and release of IFN-γ, IL-12 also has a role in activating natural killer cells, acts as an anti-angiogenic factor and it is important in the reactivation and survival of memory T cells [21]. Increasing intratumoral IL-12 may increase the immune response against cancer cells.…”

“…The IL-12 cytokine has been the subject of many clinical studies to determine its safety and efficacy as an antitumor agent, and, like IFN-α-2a and high-dose IL-2, systemic administration of IL-12 has been associated with limited efficacy and substantial toxicity [21,[26][27][28][29][30][31][32][33]. Direct administration of IL-12 into solid tumors induces a switch from a Th2 to a Th1 intratumoral immune profile in a surgical window study, but this approach is again associated with significant treatment-associated toxicity [34].…”

HBx-induced miR-21 suppresses cell apoptosis in hepatocellular carcinoma by targeting interleukin-12

“…IL-12 promotes the effective destruction of cancer cells by inducing proliferation of NK and T cells, and IL-12 enhances the generation and activity of cytotoxic T lymphocytes (CTLs) (18,19). In addition, several other mechanisms of IL-12 strongly contribute to antitumor activities (20,21), and the antitumor activity of IL-12 can be improved by its combination with various therapeutics (22,23).…”