This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Until recently, medical treatment for renal cell cancer (RCC) has focused on biological therapies designed to mobilize immune effector cells that recognize and destroy cancer (1). One biological therapy, interleukin-2 (IL-2), induces durable complete remissions (cure) but only in a minority (6%) of patients with metastatic (m) RCC (2). We have recently observed a 50% objective response rate [16% complete response (CR)] in 18 mRCC patients treated with autolotous tumor-lysate dendritic cell (DC)-vaccine, IL-2 and interferon (IFN-alpha) (10). New agents directed at disrupting the Vascular Endothelial Growth Factor (VEGF) pathways as well as other tumor proliferation and vascular signal pathways have demonstrated significant benefit in the treatment of mRCC patients (3,4,5). These new therapies can stabilize the disease or cause partial remissions, but rarely induce CRs or cures. Elevated circulating VEGF in RCC patients is associated with poor response to IL-2 and can be a cause for tumor specific immune dysregulation in this population (6,7). Blocking VEGF pathways has been demonstrated to impede regulatory/inhibitory T cells and re-establish immune competency (8). Building on observations in our DC vaccine clinical trial and new understanding of VEGF pathways we propose to test whether VEGF blockade combined with immunotherapy can enhance clinical outcome for mRCC patients (9).
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