Immunotherapy of patients with hormone-refractory prostate carcinoma pre-treated with interferon-gamma and vaccinated with autologous PSA-peptide loaded dendritic cells--a pilot study.
OBJECTIVE
We conducted a pilot trial to assess the feasibility and tolerability of a prime/boost vaccine strategy using interferon-gamma (IFN-gamma) and autologous dendritic cells (DCs) pulsed with HLA-A2-specific prostate-specific antigen (PSA) peptides (PSA-1 [141-150]; PSA-2 [146-156]; PSA-3 [154-163]) for the treatment of 12 patients with hormone refractory prostate carcinoma.


METHODS
All patients were vaccinated four times with intracutaneously injected PSA-peptide loaded DCs after subcutaneous administration of IFN-gamma 2 hr before DC administration (50 microg/m(2) body surface). Objectives were safety, clinical benefit, clinical and biochemical response, quality of life, and immunological parameters.


RESULTS
The vaccination was well tolerated without any vaccination-associated adverse events. One partial and one mixed responder were identified, four patients showed stable diseases. Two patients had a decrease and four a slow-down velocity slope in the PSA serum level. All responders showed a positive DTH-response, but only two a slight increase in PSA-peptide specific T-lymphocytes.


CONCLUSIONS
The immunotherapy with IFN-gamma and PSA-peptide loaded DCs was feasible and well tolerated. The observed responses imply a potential antitumor activity.
Hildenbrand
B
B
Tumor Biology Center, Freiburg, Germany. hildenbrand@tumorbio.uni-freiburg.de
Sauer
B
B
Kalis
O
O
Stoll
C
C
Freudenberg
M A
MA
Niedermann
G
G
Giesler
J M
JM
Jüttner
E
E
Peters
J H
JH
Häring
B
B
Leo
R
R
Unger
C
C
Azemar
M
M
D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods*; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017430:Prostate-Specific Antigen / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D011788:Quality of Life
D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen