Identification of multifunctional cytotoxic T-cell subsets as immune correlates with clinical outcomes in a phase II study of AGS-003, an autologous dendritic cell-based therapy administered to patients with newly diagnosed, metastatic RCC.

80 Background: AGS-003 is an autologous dendritic cell (DC) immunotherapy prepared from matured monocyte-derived DC co-electroporated with the subject’s own amplified tumor RNA and synthetic CD40L RNA. The mechanism of action (MOA) of AGS-003 was evaluated in combination with sunitinib for treatment of advanced renal cell carcinoma (RCC) in AGS-003-006, an open label phase II trial including subjects with newly diagnosed, unfavorable-risk, metastatic clear cell RCC. The goal of the immune monitoring platform is to identify unique cytotoxic T-cell (CTL) signatures that correlate with clinical outcome in subjects receiving AGS-003 in combination with sunitinib. Methods: Multiparametric flow cytometry was used to identify tumor-reactive CTL subsets induced by AGS-003 based on combinatorial expression patterns of surface markers CD28, CD45RA, CD27 and CCR7. Moreover, further partitioning of each CTL subset identified combinatorial expression patterns of Markers of Immune Function (MIFs) defined as cytokines (...