Zhuang Zhi-Xiang, Shen Li-Qin, Shi Yang, Lu Xiao, Shi Hong-Zhen
Department of Oncology, The Second Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215004, China.
Zhonghua Nan Ke Xue. 2010 Aug;16(8):698-704.
To investigate the clinical safety and effects of auto-dendritic cells pulsed with HLA-A201-binding peptides prostate-specific antigen (PSA) , prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP) in the treatment of hormone-refractory metastatic prostate cancer (HRPC).
Sixteen HRPC patients with positive HLA-A201 were enrolled and their monocytes isolated and induced into dendritic cells with the combination of rhGM-CSF and rhIL4. The patients were inoculated subcutaneously near the inguinal region with auto-DCs pulsed with peptides PSA (KLQCVDLHV) , PSMA (ALDVYNGL L) and PAP (LLHETDSAV) every 2 weeks for 4 times, and the immunological and clinical responses were examined within 1 -2 weeks after the final vaccination.
Vaccination of dendritic cells was well tolerated and no toxicity was observed. The cytokine levels in the serum such as IL-2, IL-12 and IFN-gamma were significantly increased after the vaccination (P < 0.01). The delayed type hyper- sensitivity (DTH) test was positive in 4 of the patients (4/11), the percentage of antigen-special IFN-gamma+ CD8+ T increased in 5 (5/11), the level of the tumor marker PSA decreased in 6 (6/16) , hydrops abdominis reduced in 1 (1/16), and the size of the cervical lymph node lessened in 1 (1/16). Three patients showed partial remission (PR), 7 stability of the disease (SD), and the other 6 progression of the disease (PD).
Auto-DC vaccines loaded with PSA, PSMA and PAP peptides, capable of eliciting specific immune responses in HRPC patients, is a safe and effective option for the treatment of advanced HRPC.
探讨用与HLA - A201结合的肽（前列腺特异性抗原（PSA）、前列腺特异性膜抗原（PSMA）和前列腺酸性磷酸酶（PAP））脉冲处理的自体树突状细胞治疗激素难治性转移性前列腺癌（HRPC）的临床安全性和疗效。
纳入16例HLA - A201阳性的HRPC患者，分离其单核细胞，并用重组人粒细胞巨噬细胞集落刺激因子（rhGM - CSF）和重组人白细胞介素4（rhIL4）联合诱导为树突状细胞。患者每2周在腹股沟区附近皮下接种用肽PSA（KLQCVDLHV）、PSMA（ALDVYNGL L）和PAP（LLHETDSAV）脉冲处理的自体树突状细胞，共接种4次，并在最后一次接种后1 - 2周内检测免疫和临床反应。
树突状细胞接种耐受性良好，未观察到毒性。接种后血清中白细胞介素2（IL - 2）、白细胞介素12（IL - 12）和干扰素γ（IFN - γ）等细胞因子水平显著升高（P < 0.01）。11例患者中有4例迟发型超敏反应（DTH）试验呈阳性，5例（5/11）抗原特异性IFN - γ + CD8 + T细胞百分比增加，16例中有6例（6/16）肿瘤标志物PSA水平下降，1例（1/16）腹腔积液减少，1例（1/16）颈部淋巴结大小减小。3例患者出现部分缓解（PR），7例疾病稳定（SD），另外6例疾病进展（PD）。
负载PSA、PSMA和PAP肽的自体树突状细胞疫苗能够在HRPC患者中引发特异性免疫反应，是治疗晚期HRPC的一种安全有效的选择。
