NE-AUA 2006 Annual Meeting, September 28 - 30, 2006, The Westin Hotel & Rhode Island Convention Center Providence, Rhode Island
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Immunologic Effects and Promising Clinical Responses of Autologous Dendritic Cell Vaccine in Combination with Interleukin-2 and Interferon-α-2a in Patients with Metastatic Renal Cell Carcinoma
Thomas Schwaab, MD PhD, Todd Crocenzi, MD, Jan Fisher, MS, John Seigne, MB, FRCSI, Marc Ernstoff, MD.
Dartmouth-Hitchcock Medical Center, Lebanon, NH,

Background: Immunotherapeutic trials using Dendritic Cells (DC) have produced disappointing clinical results. Yet, their immunologic potential is intriguing. We hypothesized that intranodal DC vaccine and IL-2/ IFN-α therapy decreases immune inhibition and increases tumor-specific immune activation in renal cell carcinoma (RCC) patients. We now present updated clinical data and immunologic results from a Phase II trial using an intranodal DC vaccine.
Material And Methods: DC are isolated from peripheral blood mononuclear cells obtained via leukapheresis from consented patients with metastatic RCC. DC are grown in our cell-processing laboratory using IL-4 and GM-CSF. DC are pulsed with autologous tumor lysate and matured with TNF-α. A treatment cycle consists of pulsed and matured DC injected into inguinal lymphnodes at 1x107/ml, followed the next day by intravenous IL-2 (18MiU/m2) for 5 days and 3 subcutaneous injections of IFN-α (6MiU) every other day for a total of 5 cycles. Biological responses are determined using tumor-specific T cell precursor-frequency assays and redirected cytotoxicity assays.
Results: Between 01/2004 and 12/2005, 13 patients with metastatic RCC were enrolled into this phase II trial. All patients were injected with 1x107 pulsed DC. Patients received between 2 and 5 vaccine injections. Inguinal lymph node injection was very well tolerated with only minor local swelling and discomfort. At this point, 2 patients (15.8%) exhibit a complete response, 4 patients (30.8%) exhibit a partial response, 5 patients (38.5%) show stable disease and 2 patients (15.4%) have progressed. This results in an overall response rate of 46.6%. Clinical responses are persistent up to 17 months. Early immunologic data is presented on patients who received at least 3 vaccinations. All 4 evaluated patients showed treatment-related increases in tumor-specific CD4+ T cell precursors. Three of these 4 patients showed partial clinical responses. In a redirected cytotoxicity assay, a treatment-related increase in CD8+ T cell lytic activity was observed in 3 out of 6 patients (50%). Two of these patients showed partial clinical responses, the third patient showed stable disease.
Conclusions: As previously reported, autologous intranodal DC-vaccine holds great promise. We now present immunologic data supporting these clinical results. However, the lack of consistent increase in cytolytic T cell activity may represent the heterogeneity of the T Cell Receptor Complex. Because of the complexity of the immune system and the multi-faceted nature of tumor immune escape, an effective immunotherapy for RCC should not be limited to one single target pathway or tumor immune escape mechanism


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