Improved overall survival in dendritic cell vaccination-induced immunoreactive subgroup of advanced melanoma patients

Abstract

Background: We present our experience of therapeutic vaccination using dendritic cells (DC) pulsed with autologous tumor antigens in patients with advanced melanoma. Methods: Twenty-one pretreated advanced melanoma patients were vaccinated with autologous DC pulsed with 100 μg/ml of autologous-tumor-lysate (ATL) or - homogenate (ATH) and 50 μg/ml of keyhole limpet hemocyanin (KLH). The first 8 patients were treated subcutaneously or intradermally with immature-DC (iDC)(range 4.5 - 82 × 106) and the remaining 13 intradermally with in vitro matured DC (mDC) (range 1.2-26 × 106). Subcutaneous interleukin-2 (3 × 106 IU) was administered from days 3 to 7 of each treatment cycle. Results: Three of the 8 iDC patients obtained stabilizations (SD), each of 6 months' duration. The 13 mDC patients showed 1 complete response (8 months), 1 partial response (3 months), 2 mixed responses (6 and 12 months) and 3 SID (9, 7+, and 3+ months). Overall responses (OR) were observed in 4/21 (19%) patients, or 4/13 (30.7%) considering mDC treatment only. 10/21 (47.6%) patients showed non progressive disease (NPD), with 7/13 (53.8%) cases of NPD for mDC-treated patients. No major toxicities were observed. The positive delayed-type hypersensitivity (DTH) test to ATL/ATH and/or KLH correlated with increased overall survival (OS). Median OS was 24 months (range 3 - 45) for the 10 DTH-positive (1 iDC and 9 mDC) and 5 months (range 3-14) for the 11 DTH-negative patients (P < 0.001). The in vitro evaluation of gamma IFN-secreting T-cells in 10 patients showed good correlation with both DTH (75%) and clinical outcome (70%). Conclusion: Vaccination using DC pulsed with ATL/ATH and KLH in advanced melanoma patients is well tolerated and can induce a clinical response, especially when mDC are used. Successful immunization, verified by positive DTH, leads to longer survival. © 2006 Ridolfi et al; licensee BioMed Central Ltd.