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R. Parihar, P. Nadella, A. Lewis, R. Jensen, C. De Hoff, J. E. Dierksheide, A. M. VanBuskirk, C. M. Magro, D. C. Young, C. L. Shapiro and W. E. Carson III, “A Phase I Study of Interleukin 12 with Trastuzumab in Patients with Human Epidermal Growth Factor Receptor-2-Overexpressing Malignancies: Analysis of Sustained Interferon Gamma Production in a Subset of Patients,” Clinical Cancer Research, Vol. 10, No. 15, 2004, pp. 5027-5037. doi:10.1158/1078-0432.CCR-04-0265

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• TITLE: Low Dose of IL-12 Stimulates T Cell Response in Cultures of PBMCs Derived from Non Small Cell Lung Cancer Patients

  AUTHORS: Lucia D’Amico, Enrico Ruffini, Riccardo Ferracini, Ilaria Roato

  KEYWORDS: Interleukin-12; Immuno-Modulation; T Helper; T Regulatory; Anti-Tumor Immune Response

  JOURNAL NAME: Journal of Cancer Therapy, Vol.3 No.4A, September 12, 2012

  ABSTRACT: Cancer induces tolerance by suppressing immune function, modulating the T helper activity and causing an imbalance of cytokines produced by T cells. IL-12 is an immune regulatory cytokine with potent anti-tumor activity and its signalling network leads to polarization of na?ve CD4+ T cells into Th1. In pre-clinical studies, administration of recombinant IL-12 by intravenous injection or IL-12 plasmid DNA by intra-tumoral injection showed some anti-tumor effects, measurable immunological responses, but also important dose-dependent side effects. We investigated the ability of low doses of IL-12 to modulate the T cell subpopulations in cultures of PBMCs derived from Non Small Lung Cancer (NSCLC) patients and to induce lysis of lung adenocarcinoma cells by T cells. PBMCs were stimulated with different doses of IL-12 and T cell phenotype was evaluated. IL-12 at 0.01 pg/ml significantly increased the number of CD4 and CD8 T cells, in particular of CD4/IFNγ producing cells. IL-12 did not stimulate T regulatory, but it increased the lysis of lung adenocarcinoma cells induced by T cells. Our results showed that low doses of IL-12 modulates T cell sub-populations in vitro and it increased their lytic activity on adenocarcinoma cells, thus we hypothesize the use of low dose of IL-12 as a therapeutic tool against pathologies characterized by a T cell imbalance, in order to promote an immuno-modulation.