Abstract 1239: Characterization of the response of human T cells to an agonist human anti-CD27 mAb.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC CD27, a member of the tumor necrosis factor receptor super family (TNFRSF), is constitutively expressed on the majority of mature T cells, memory B cells, and a portion of NK cells. Previously we have reported antitumor and immunological properties of the fully human anti-CD27 mAb 1F5 in huCD27 transgenic mouse models. Here we report the 1F5-induced immune modulation of isolated human T cells. In vitro activation of peripheral blood-derived T cells from different healthy volunteers with mAb 1F5 showed that crosslinking of CD27 in the presence of CD3 stimulation (OKT3 mAb) was essential to elicit proliferation and a broad spectrum of cytokine release. Analysis of this response on a multiplex cytokine array system revealed a Th1-biased cytokine profile (IFNγ, IL-2 and TNFα). Interestingly, IL-13 was the only major Th2 cytokine that was detected in large amounts. Furthermore, activation of isolated CD4+ and CD8+ T cells showed both subsets contributed to the IL-13 secretion with higher secretion amounts detected in the CD4+ T cell cultures. Altogether, the data suggest an agonistic role for 1F5 characterized predominantly by a defined antigen-receptor coupled Th1 effector response. IL-13, which appears later after stimulation may represent immune regulatory modulation as has been described in activation of the related 4-1BB co-stimulation pathway. Transcriptional profiling by microarray RNA hybridization is underway to map specific and global gene expression changes following 1F5 modulation of T cells. Citation Format: Karuna Sundarapandiyan, Laura Vitale, Biwei Zhao, Thomas O'Neill, Henry Marsh, Venky Ramakrishna, Tibor Keler. Characterization of the response of human T cells to an agonist human anti-CD27 mAb. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1239. doi:10.1158/1538-7445.AM2013-1239