To date, clinical trials using Dendritic Cell (DC) vaccinations have been disappointing. Yet, their immunologic potential remains intriguing. We recently presented data from a Phase II trial using intranodal DC vaccine combined with Interleukin-2 and Interferon-α therapy in metastatic renal cell carcinoma (RCC) patients. A challenge for immunotherapy is to maintain long-term responses. We here present updated clinical data on patients showing clinical responses.
Consented and eligible patients with measurable metastatic RCC were treated. Monocytes, isolated from peripheral blood via leukapheresis, were cultured into mature DC using cytokines and autologous tumor lysate. A treatment cycle consisted of intranodal injection of 1x10⁷/ml DC-vaccines, followed the next day by 5-day infusion of intravenous IL-2 (18MiU/m²) and 3 subcutaneous injections of IFN-α 2a (6MiU) every other day for a total of 5 cycles.
Between 01/2004 and 08/2006, 18 patients with metastatic RCC were enrolled into this phase II trial. Toxicities were consistent with standard IL-2 side effects. Three patients (16.7%) exhibited a complete response, 5 patients (27.8%) a partial response, 8 patients (27.8%) showed stable disease and 2 patients (16.7%) progressed. This resulted in an overall objective clinical response rate of 44.5%. Updated clinical data showed that complete responses lasted between 2 and 26 months (Median: 8 months, Mean: 11.8 months). Partial responses lasted between 3 and 22 months (Median: 8 months, Mean: 9.8 months). The overall median time to progression for clinical responders was 5 months and the Mean was 10.5 months. Clinical responses were seen in both visceral (bone, lung, liver, adrenal) and lymph node based disease sites.
The objective response and durability of response seen in this trial suggest significant interaction between DC vaccination and cytokine therapy. The intranodal route may be advantageous in inducing memory T cell responses.