PSA、PSMA、PAP多肽联合致敏自体DC治疗HRPC的临床研究  

Auto-dendritic cell vaccines pulsed with PSA,PSMA and PAP peptides for hormone-refractory prostate cancer

作　　者：庄志祥[1] 沈丽琴[1] 史央 陆晓 时宏珍 

机构地区：[1]苏州大学附属第二医院肿瘤科,江苏苏州215004 [2]南京得康生物技术有限公司,江苏南京210019

出　　处：《中华男科学杂志》2010年第8期698-704,共7页National Journal of Andrology

摘　　要：目的:观察前列腺特异性抗原(PSA)、前列腺特异性膜抗原(PSMA)与前列腺酸性磷酸酶(PAP)多肽联合致敏自体树突状细胞(DC)治疗激素难治性前列腺癌(HRPC)的安全性与有效性。方法:选择HLA-A201阳性HRPC患者16例,分离患者外周血中单核细胞,加入重组人粒细胞集落刺激因子(rhGM-CSF)与白介素(rhIL-4)诱导成DC。用PSA(KLQCVDLHV)、PSMA(ALDVYNGLL)与PAP(LLHETDSAV)3种多肽联合冲击DC后近腹股沟淋巴结富集区皮内多点接种致敏DC,隔周1次,共进行4次接种,于最后1次接种后1～2周内进行免疫学与近期临床疗效的监测。结果:未见1例出现Ⅱ级以上不良反应(寒颤、发烧、注射部位红肿、皮疹等)。患者接种DC后外周血中IL-2、IL-12和IFN-γ水平呈明显上升趋势(P<0.01);迟发型超敏反应(DTH)试验阳性率为36.4%(4/11);5例患者外周抗原特异性IFN-γ+CD8+T细胞比例明显增加(5/11);6例患者PSA水平下降(6/16);1例患者腹腔积液减少;1例患者颈部淋巴结转移灶缩小。3例患者临床反应达到部分缓解(PR),7例患者稳定(SD),6例患者进展(PD)。结论:PSA、PSMA和PAP多肽联合负载自体DC免疫治疗方法可明显改善HRPC患者免疫功能,有效激发特异性T细胞免疫应答,控制并缓解病情,是治疗晚期HRPC的一种安全与有效的手段。Objective ：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）. Methods ：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 rhIL-4. 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. Results ：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-γ were significantly increased after the vaccination （P 0.01）. The delayed type hypersensitivity （DTH） test was positive in 4 of the patients （4/11）,the percentage of antigen-special IFN-γ＋ 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）. Conclusion ：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.

关 键 词：树突状细胞 激素难治性前列腺癌 免疫治疗 前列腺特异性抗原 前列腺特异性膜抗原 前列腺酸性磷酸酶 

分 类 号：R737.25[医药卫生—肿瘤]