Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma

• Published in: Journal of translational medicine 2010-09, Vol.8 (1), p.89-89, Article 89
• Main Authors: Ribas, Antoni, Camacho, Luis H, Lee, Sun Min, Hersh, Evan M, Brown, Charles K, Richards, Jon M, Rodriguez, Maria Jovie, Prieto, Victor G, Glaspy, John A, Oseguera, Denise K, Hernandez, Jackie, Villanueva, Arturo, Chmielowski, Bartosz, Mitsky, Peggie, Bercovici, Nadège, Wasserman, Ernesto, Landais, Didier, Ross, Merrick I
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Autoimmune diseases; Cancer; Cancer cells; Cancer therapies; Cancer vaccines; Cancer Vaccines - administration & dosage; Cancer Vaccines - adverse effects; Cancer Vaccines - therapeutic use; Care and treatment; Cell Line, Tumor; Clinical medicine; Clinical trials; Dendritic cells; Dendritic Cells - cytology; Female; Flow Cytometry; Health aspects; Humans; Immune system; Interferon-gamma - metabolism; Lysosomal-Associated Membrane Protein 1 - metabolism; Lysosomal-Associated Membrane Protein 2 - metabolism; Male; Melanoma; Melanoma - metabolism; Melanoma - pathology; Melanoma - therapy; Middle Aged; Neoplasm Metastasis; Physiological aspects; Prevention; Treatment Outcome; Vaccines
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/1479-5876-8-89

Several single center studies have provided evidence of immune activation and antitumor activity of therapeutic vaccination with dendritic cells (DC) in patients with metastatic melanoma. The efficacy of this approach in patients with favorable prognosis metastatic melanoma limited to the skin, subcutaneous tissues and lung (stages IIIc, M1a, M1b) was tested in a multicenter two stage phase 2 study with centralized DC manufacturing. The vaccine (IDD-3) consisted 8 doses of autologous monocyte-derived matured DC generated in serum-free medium with granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-13 (IL-13), pulsed with lysates of three allogeneic melanoma cell lines, and matured with interferon gamma. The primary endpoint was antitumor activity. Among 33 patients who received IDD-3 there was one complete response (CR), two partial responses (PR), and six patients had stable disease (SD) lasting more than eight weeks. The overall prospectively defined tumor growth control rate was 27% (90% confidence interval of 13-46%). IDD-3 administration had minimal toxicity and it resulted in a high frequency of immune activation to immunizing melanoma antigens as assessed by in vitro immune monitoring assays. The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma. NCT00107159.