Abstract 2573: The immunocytokine NHS-IL12 as a potential cancer therapeutic

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Targeted delivery of IL-12 might make this cytokine a safer, more effective cancer therapeutic. Here we evaluated whether fusing IL-12 to a tumor necrosis-targeting human IgG1 (NHS76) could improve its anti-tumor efficacy in vivo. In vivo imaging and immunohistochemistry staining were used to assess the ability of this novel immunocytokine (NHS-IL12) to target murine tumors. The anti-tumor efficacy of NHS-IL12 was examined at various doses and treatment schedules. Immune cell subset-depleting antibodies, flow cytometric methods, and in vitro cytotoxicity and ELISA assays were used to investigate the mechanisms of action of NHS-IL12. This immunocytokine was investigated in several models and in all cases NHS-IL12 outperformed recombinant IL-12 in anti-tumor activity. Depletion of immune cell subsets revealed that the anti-tumor activity depends primarily on CD8+ cells; mice that had complete tumor regression following NHS-IL12 treatment displayed durable anti-tumor memory responses. Combining NHS-IL12 treatment with a cancer vaccine, radiation, or chemotherapy resulted in greater anti-tumor effects than each individual therapy alone. These preclinical findings provide a rationale for the clinical testing of this immunocytokine, both as a single agent and in combination with vaccines, radiation, and chemotherapy. NHS-IL12 is currently being evaluated in a Phase 1 clinical trial ([NCT01417546][1]). Citation Format: Jonathan K. Fallon, Robert Tighe, Amanda J. Lyon, Helen Sabzevari, Jeffrey Schlom, John W. Greiner. The immunocytokine NHS-IL12 as a potential cancer therapeutic. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2573. doi:10.1158/1538-7445.AM2014-2573 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01417546&atom=%2Fcanres%2F74%2F19_Supplement%2F2573.atom