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


BACKGROUND
NCT00107159.
Ribas
Antoni
A
University of California Los Angeles (UCLA), CA, USA. aribas@mednet.ucla.edu
Camacho
Luis H
LH
Lee
Sun Min
SM
Hersh
Evan M
EM
Brown
Charles K
CK
Richards
Jon M
JM
Rodriguez
Maria Jovie
MJ
Prieto
Victor G
VG
Glaspy
John A
JA
Oseguera
Denise K
DK
Hernandez
Jackie
J
Villanueva
Arturo
A
Chmielowski
Bartosz
B
Mitsky
Peggie
P
Bercovici
Nadège
N
Wasserman
Ernesto
E
Landais
Didier
D
Ross
Merrick I
MI
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1 / Q000378:metabolism; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016896:Treatment Outcome
D019496:Cancer Vaccines; D052118:Lysosomal-Associated Membrane Protein 1; D052119:Lysosomal-Associated Membrane Protein 2; D007371:Interferon-gamma