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

Journal of Translational Medicine

Research

Ernesto Wasserman¹  Evan M Hersh²  Charles K Brown³  Peggie Mitsky⁴  Didier Landais⁴  Sun Min Lee⁴  Nadège Bercovici⁴  Jon M Richards⁵  Maria Jovie Rodriguez⁶  Luis H Camacho⁶  Merrick I Ross⁶  Victor G Prieto⁶  Denise K Oseguera⁷  Bartosz Chmielowski⁷  John A Glaspy⁷  Arturo Villanueva⁷  Antoni Ribas⁷  Jackie Hernandez⁷ 

[1] AAI Pharma Inc, San Antonio, TX, USA;Arizona Cancer Center, Tucson, AZ, USA;Hillman Cancer Center, Pittsburgh, PA, USA;IDM Pharma Inc. (IDM), Irvine, CA, USA;Lutheran General Cancer Care Centre, Park Ridge, IL, USA;MD Anderson Cancer Center, Houston, TX, USA;University of California Los Angeles (UCLA), CA, USA;

关键词: Melanoma;    Peripheral Blood Mononuclear Cell;    Metastatic Melanoma;    Ipilimumab;    Granulocyte Macrophage Colony Stimulate Factor;   

DOI  :  10.1186/1479-5876-8-89

 received in 2010-05-27, accepted in 2010-09-27,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundSeveral 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.MethodsThe 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.ResultsAmong 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.ConclusionsThe administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma.Clinical trial registrationNCT00107159.

【 授权许可】

CC BY   
© Ribas et al; licensee BioMed Central Ltd. 2010