Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells.
OBJECTIVE
Provenge (Dendreon Corp, Seattle, WA) is an immunotherapy product consisting of autologous dendritic cells loaded ex vivo with a recombinant fusion protein consisting of prostatic acid phosphatase (PAP) linked to granulocyte-macrophage colony-stimulating factor. Sequential phase I and phase II trials were performed to determine the safety and efficacy of Provenge and to assess its capacity to break immune tolerance to the normal tissue antigen PAP.


METHODS
All patients had hormone-refractory prostate cancer. Dendritic-cell precursors were harvested by leukapheresis in weeks 0, 4, 8, and 24, loaded ex vivo with antigen for 2 days, and then infused intravenously over 30 minutes. Phase I patients received increasing doses of Provenge, and phase II patients received all the Provenge that could be prepared from a leukapheresis product.


RESULTS
Patients tolerated treatment well. Fever, the most common adverse event, occurred after 15 infusions (14.7%). All patients developed immune responses to the recombinant fusion protein used to prepare Provenge, and 38% developed immune responses to PAP. Three patients had a more than 50% decline in prostate-specific antigen (PSA) level, and another three patients had 25% to 49% decreases in PSA. The time to disease progression correlated with development of an immune response to PAP and with the dose of dendritic cells received.


CONCLUSIONS
Provenge is a novel immunotherapy agent that is safe and breaks tolerance to the tissue antigen PAP. Preliminary evidence for clinical efficacy warrants further exploration.
Small
E J
EJ
Department of Medicine and Urology, University of California San Francisco Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA. smalle@medicine.ucsf.edu
Fratesi
P
P
Reese
D M
DM
Strang
G
G
Laus
R
R
Peshwa
M V
MV
Valone
F H
FH
D000135:Acid Phosphatase / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000230:Adenocarcinoma / Q000276:immunology / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000912:Antibodies, Neoplasm / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active / Q000009:adverse effects / Q000379:methods; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000135:Acid Phosphatase