Monitoring T-cell responses in a phase II study of AGS-003, an autologous dendritic cell-based therapy in patients with newly diagnosed advanced stage renal cell carcinoma in combination with sunitinib.

Abstract 2532 Background: Dendritic cells (DC) are a powerful tool for stimulating cell-mediated immunity through the effects of CD4(+) and CD8(+) T cells. This phase II study investigated AGS-003, an autologous amplified tumor RNA-loaded DC-based immunotherapy in patients with RCC in combination with sunitinib. AGS-003 stimulates proliferation of CD28 expressing cytotoxic T lymphocytes (CTL), targeted directly to autologous RCC tumor antigens. While sunitinib is capable of inducing tumor regression through inhibition of VEGF activity, it also possesses non-specific immune modulatory effects, which include a noted decrease in regulatory T cells. Therefore, the combination of AGS-003 and sunitinib could result in synergistic effects over that which could be achieved with either modality alone. Immune monitoring (IM) analysis using multiparametric flow cytometry was performed on PBMC isolated from blood draws collected prior to treatment and after treatment with AGS-003 during combination administration with sunitinib. Results revealed that for all subjects tested, there was a decrease in the percentage of T regulatory cells during combination treatment with AGS-003 and sunitinib compared to pre-therapy baseline levels. With the exception of one outlier, there was a correlation between decreased regulatory T cells and PFS (r(2)=0.7662). Also, patients treated concurrently with AGS-003 in the presence of sunitinib were able to expand CD28(+) memory CTL with a broad range of effector functions. The expansion of tumor antigen-reactive CD28(+) CTL revealed a trend between PFS and the change in CD28(+) effector memory CTL post-treatment. Nine of 11 subjects with PFS of >10 months demonstrated CTL population increases whereas 2 of 4 subjects with PFS