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
Tumor Biology Center, Freiburg, Germany.
Prostate. 2007 Apr 1;67(5):500-8. doi: 10.1002/pros.20539.
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.
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.
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.
The immunotherapy with IFN-gamma and PSA-peptide loaded DCs was feasible and well tolerated. The observed responses imply a potential antitumor activity.
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。
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。
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。
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。
