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

Antoni Ribas, Luis H. Camacho, Sun M. Lee, Evan M Hersh, Charles K. Brown, Jon M. Richards, Maria J. Rodriguez, Victor G. Prieto, John A. Glaspy, Denise K. Oseguera, Jackie Hernandez, Arturo Villanueva, Bartosz Chmielowski, Peggie Mitsky, Nadège Bercovici, Ernesto Wasserman, Didier Landais, Merrick I. Ross

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Background: 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.Methods: 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.Results: 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.Conclusions: The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma.Clinical trial registration: NCT00107159.

Original languageEnglish (US)
Article number89
JournalJournal of Translational Medicine
Volume8
DOIs
StatePublished - Sep 27 2010

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Dendritic Cells
Melanoma
Cells
Cell Line
Tumors
Chemical activation
Melanoma-Specific Antigens
Interleukin-13
Serum-Free Culture Media
Granulocyte-Macrophage Colony-Stimulating Factor
Immunologic Monitoring
Interferon-gamma
Subcutaneous Tissue
Toxicity
Assays
Skin
Vaccines
Tissue
Monocytes
Neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma. / Ribas, Antoni; Camacho, Luis H.; Lee, Sun M.; Hersh, Evan M; Brown, Charles K.; Richards, Jon M.; Rodriguez, Maria J.; 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.

In: Journal of Translational Medicine, Vol. 8, 89, 27.09.2010.

Research output: Contribution to journalArticle

Ribas, A, Camacho, LH, Lee, SM, Hersh, EM, Brown, CK, Richards, JM, Rodriguez, MJ, Prieto, VG, Glaspy, JA, Oseguera, DK, Hernandez, J, Villanueva, A, Chmielowski, B, Mitsky, P, Bercovici, N, Wasserman, E, Landais, D & Ross, MI 2010, 'Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma', Journal of Translational Medicine, vol. 8, 89. https://doi.org/10.1186/1479-5876-8-89
Ribas, Antoni ; Camacho, Luis H. ; Lee, Sun M. ; Hersh, Evan M ; Brown, Charles K. ; Richards, Jon M. ; Rodriguez, Maria J. ; 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. / Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma. In: Journal of Translational Medicine. 2010 ; Vol. 8.
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T1 - Multicenter phase II study of matured dendritic cells pulsed with melanoma cell line lysates in patients with advanced melanoma

AU - Ribas, Antoni

AU - Camacho, Luis H.

AU - Lee, Sun M.

AU - Hersh, Evan M

AU - Brown, Charles K.

AU - Richards, Jon M.

AU - Rodriguez, Maria J.

AU - Prieto, Victor G.

AU - Glaspy, John A.

AU - Oseguera, Denise K.

AU - Hernandez, Jackie

AU - Villanueva, Arturo

AU - Chmielowski, Bartosz

AU - Mitsky, Peggie

AU - Bercovici, Nadège

AU - Wasserman, Ernesto

AU - Landais, Didier

AU - Ross, Merrick I.

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Y1 - 2010/9/27

N2 - Background: 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.Methods: 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.Results: 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.Conclusions: The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma.Clinical trial registration: NCT00107159.

AB - Background: 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.Methods: 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.Results: 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.Conclusions: The administration of matured DC loaded with tumor lysates has significant immunogenicity and antitumor activity in patients with limited metastatic melanoma.Clinical trial registration: NCT00107159.

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