Abstract 1350: The combination of a murine iNKT cell-activating antibody and IL-12 exhibits antitumor activity in a mouse melanoma model

Abstract Invariant natural killer T (iNKT) cells are innate-like T cells with an invariant iTCR with potent anti-tumor activity. Current anti-tumor clinical trials using the iNKT cell ligand, a-galactosylceramide (a-GalCer) have had limited success. One major limitation of a-GalCer-based therapies is the bioavailability of lipid drugs and current therapies require isolation and a-GalCer loading of dendritic cells prior to administration (Richter et al Blood 121:423, 2013). We have engineered a murine iNKT TCR-targeting monoclonal antibody (NKT14m) that activates iNKT cells directly without dendritic cells or glycolipids. We have evaluated the in vivo anti-tumor efficacy with the established B16 mouse melanoma model. Based on preliminary results that the potency of NKT14m is less than that of a-GalCer, we reasoned that the addition of IL-12 stimulation would be beneficial for iNKT cell activation (Yue et al PNAS 102:11811, 2005). Currently, the toxicity of IL-12 has restricted its use in clinical trials. We evaluated a non-toxic dose of IL-12 alone and in combination with NKT14m. C57BL/6 mice were injected with 400K B16F10 melanoma cells on Day 0. On Day 2 they were divided into untreated, IL-12 treated (0.1 ug/mouse/day for 12 days), NKT14m treated (100 ug/mouse once on Day 2) and the combination of NKT14m+IL-12 using the same dose regimens. On Day 14 mice were sacrificed and lung tumors counted. We detected a synergistic effect in the combination of NKT14m+IL-12 (Table 1). These findings represent a new paradigm of iNKT cell activation for their anti-tumor function. Table 1 - Lung Tumors in Treatment GroupsExperimental GroupsControlIL-12NKT14mIL-12+NKT14mNumbers of metastatic tumors150+/-67117+/-2555+/-2923+/-10 Citation Format: Weiming Yuan, Xiangshu Wen. The combination of a murine iNKT cell-activating antibody and IL-12 exhibits antitumor activity in a mouse melanoma model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1350. doi:10.1158/1538-7445.AM2015-1350