用γ-干扰素预处理并用负载自体前列腺特异性抗原(PSA)肽的树突状细胞进行疫苗接种的激素难治性前列腺癌患者的免疫治疗——一项试点研究。
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.
作者信息
Hildenbrand B, Sauer B, Kalis O, Stoll C, Freudenberg M A, Niedermann G, Giesler J M, Jüttner E, Peters J H, Häring B, Leo R, Unger C, Azemar M
机构信息
Tumor Biology Center, Freiburg, Germany.
出版信息
Prostate. 2007 Apr 1;67(5):500-8. doi: 10.1002/pros.20539.
PURPOSE
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.
PATIENTS AND 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.
CONCLUSION
The immunotherapy with IFN-gamma and PSA-peptide loaded DCs was feasible and well tolerated. The observed responses imply a potential antitumor activity.
目的
我们开展了一项初步试验,以评估使用干扰素-γ(IFN-γ)和负载 HLA-A2 特异性前列腺特异性抗原(PSA)肽(PSA-1 [141-150];PSA-2 [146-156];PSA-3 [154-163])的自体树突状细胞(DC)进行初免/加强疫苗策略治疗 12 例激素难治性前列腺癌患者的可行性和耐受性。
患者与方法
所有患者在皮下注射 IFN-γ 2 小时后(50 μg/m²体表面积),皮内注射负载 PSA 肽的 DC,共接种 4 次。观察指标包括安全性、临床获益、临床及生化反应、生活质量和免疫参数。
结果
疫苗接种耐受性良好,未出现任何与接种相关的不良事件。确定了 1 例部分缓解者和 1 例混合缓解者,4 例患者疾病稳定。2 例患者 PSA 血清水平下降,4 例患者 PSA 血清水平增速减缓。所有缓解者均表现出阳性迟发型超敏反应(DTH),但只有 2 例患者 PSA 肽特异性 T 淋巴细胞略有增加。
结论
IFN-γ 和负载 PSA 肽的 DC 免疫治疗可行且耐受性良好。观察到的反应提示具有潜在的抗肿瘤活性。