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Part of the book series: SpringerBriefs in Immunology ((BRIEFSIMMUN))

Abstract

Preclinical studies with IL-12 in animal models of experimental oncology have shown very encouraging results and acceptable toxicities and prompted the use of IL-12 in cancer patients in the mid-90s of the last century. On the basis of the largest registry of clinical studies in the world (http://www.clinicaltrials.gov), 58 clinical trials, in which IL-12-based therapy was/is used for treatment of patients with various types of cancers (key words for survey: IL-12, interleukin 12, hIL-12, pIL-12, INO-9012, tumor, cancer) have been identified so far. Analysis the history of these trials shows three stages of interest in the application of IL-12 in clinical oncology. Years 1996–2005 was a period of most intensive studies in which optimal treatment schedules, maximal tolerated doses of IL-12, and the most susceptible tumors were characterized. IL-12 was had a very narrow therapeutic index and its systemic administration induced severe side effects. In fact, only few studies reported promising results with sporadic overt tumor regressions (apart from patients with AIDS-associated Kaposi sarcoma). Due to the low response to IL-12 and its high toxicity, accrual to some trials was even stopped (Motzer et al. in Journal of Interferon and Cytokine Research 21:257–263, 2001). However, after a several-year discouragement in the first decade of this century it seems that the interest in therapeutic potential of IL-12 has revived but the strategy of its use is being revised. Generally, IL-12-based therapies can be divided into three categories:

  • active nonspecific immunotherapy aimed, mainly, at activation of innate mechanisms of the antitumor response. It includes application of IL-12 alone or in combination with chemotherapy or monoclonal antibodies,

  • active specific (“vaccine”) approach in which IL-12 is used as an adjuvant in combination with more or less modified tumor cells or tumor antigen-derived peptides,

  • gene therapy, including cellular adoptive treatment and vaccination with plasmid DNA containing genes encoding targeted tumor antigens and IL-12.

While the first approach predominated in years 1996–2005, most of the recently initiated clinical trials have been concentrated on gene therapy (Fig. 3.1) (Lasek et al. in Cancer Immunology Immunotherapy 63(5):419–435, 2014). At present, twenty five IL-12-based clinical trials in cancer patients are ongoing/active (as of July 1, 2016).

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Lasek, W., Zagozdzon, R. (2016). Clinical Trials with IL-12 in Cancer Immunotherapy. In: Interleukin 12: Antitumor Activity and Immunotherapeutic Potential in Oncology. SpringerBriefs in Immunology. Springer, Cham. https://doi.org/10.1007/978-3-319-46906-5_3

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