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.

Fig. 1

An overview of the biological properties of IL-12 contributing to the antitumor activity of this cytokine (see the text for details). APC antigen-presenting cell, NK natural killer cell, Tc cytotoxic T lymphocyte, Th T helper lymphocyte, IP-10 interferon-inducible protein 10, MIG monokine induced by interferon γ

Fig. 2

Number of IL-12-based clinical trials in the field of tumor immunotherapy that have been started since 1996 and have been registered in ClinicalTrials.gov database (http://www.clinicaltrials.gov). The histogram comprises studies in which IL-12 was used alone or in combination, either as a main therapeutic or administered in an adjuvant setting including gene therapy