Vaccination of prostatectomized prostate cancer patients in biochemical relapse, with autologous dendritic cells pulsed with recombinant human PSA

被引:61
作者
Barrou, B
Benoît, GR
Ouldkaci, M
Cussenot, O
Salcedo, M
Agrawal, S
Massicard, SV
Bercovici, N
Ericson, ML
Thiounn, N
机构
[1] Hop La Pitie Salpetriere, AP HP, Serv Urol, F-75651 Paris 13, France
[2] Hop Kremlin Bicetre, AP HP, Serv Urol, Paris, France
[3] Hop St Louis, AP HP, Serv Urol, Paris, France
[4] Immuno Designed Mol, F-75545 Paris, France
[5] Hop Cochin, AP HP, Serv Urol, F-75674 Paris, France
关键词
dendritic cells; prostate-specific antigen; circulating cancer cells;
D O I
10.1007/s00262-003-0451-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This study was conducted in prostate cancer patients in biochemical relapse after radical prostatectomy, to assess the feasibility, safety, and immunogenicity of therapeutic vaccination with autologous dendritic cells (DCs) pulsed with human recombinant prostate-specific antigen (PSA) (Dendritophage-rPSA). Twenty-four patients with histologically proven prostate carcinoma and an isolated postoperative rise of serum PSA (>1 ng/ml to 10 ng/ml) after radical prostatectomy were included. The patients received nine administrations of PSA-loaded DCs by combined intravenous, subcutaneous, and intradermal routes over 21 weeks. Postbaseline blood tests were performed at months 1, 3, 6, 9, and 12 (PSA levels), at months 6 and 12 (circulating prostate cancer cells), at month 6 (anti-PSA IgG and IgM antibodies), and at up to eight time points before, during, and after immunization (PSA-specific T cells). Circulating prostate cancer cells detected in six patients at baseline were undetectable at 6 months and remained undetectable at 12 months. Eleven patients had a post-baseline transient PSA decrease on one to three occasions, predominantly occurring at month 1 (7 patients) or month 3 (2 patients). Maximum PSA decrease ranged from 6% to 39%. PSA decrease on at least one occasion was more frequent in patients with low Gleason score (p=0.016) at prostatectomy and with positive skin tests at study baseline (p=0.04). PSA-specific T cells were detected ex vivo by ELISpot for IFN-gamma in 7 patients before vaccination and in 11 patients after vaccination. Of the latter 11 patients, 5 had detectable T cells both before and during the vaccination period, 4 only during the vaccination period, while 2 patients could for technical reasons not be assessed prevaccination. No induction of anti-PSA IgG or IgM antibodies was detected. There were no serious adverse events or otherwise severe toxicities observed during the trial. Immunization with Dendritophage-rPSA was feasible and safe in this cohort of patients. An immune response specific for PSA could be detected in some patients. A notable effect was the disappearance of circulating prostate cells in all patients who were RT-PCR positive before vaccination.
引用
收藏
页码:453 / 460
页数:8
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