Immunotherapy with allotumour mRNA-transfected dendritic cells in androgen-resistant prostate cancer patients.
Here, we present results from a clinical trial employing a new vaccination method using dendritic cells (DCs) transfected with mRNA from allogeneic prostate cancer cell lines (DU145, LNCaP and PC-3). In all, 20 patients were enrolled and 19 have completed vaccination. Each patient received at least four weekly injections with 2 x 10(7) transfected DCs either intranodally or intradermally. Safety and feasibility of vaccination were determined. Immune responses were measured as delayed-type hypersensitivity and by in vitro immunoassays including ELISPOT and T-cell proliferation in pre- and postvaccination peripheral blood samples. Serum prostate-specific antigen (PSA) levels and bone scans were monitored. No toxicity or serious adverse events related to vaccinations were observed. A total of 12 patients developed a specific immune response to tumour mRNA-transfected DCs. In total, 13 patients showed a decrease in log slope PSA. This effect was strengthened by booster vaccinations. Clinical outcome was significantly related to immune responses (n = 19, P = 0.002, r = 0.68). Vaccination with mRNA-transfected DCs is safe and results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level suggests that this approach may become useful as a treatment modality for prostate cancer patients.
Mu
L J
LJ
Section for Immunotherapy, The Norwegian Radium Hospital, University of Oslo, Montebello.
Kyte
J A
JA
Kvalheim
G
G
Aamdal
S
S
Dueland
S
S
Hauser
M
M
Hammerstad
H
H
Waehre
H
H
Raabe
N
N
Gaudernack
G
G
D000368:Aged; D000728:Androgens / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D017690:Cell Transplantation; D003713:Dendritic Cells / Q000276:immunology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006968:Hypersensitivity, Delayed; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics*; D014162:Transfection
D000728:Androgens; D019496:Cancer Vaccines; D012333:RNA, Messenger; D017430:Prostate-Specific Antigen